Rinovum Subsidiary 2, LLC: Disposable Stress Urinary Incontinence Pessary Device Efficacy and Safety Study
Phase: NA
Conditions: Stress Urinary Incontinence
Sponsor: Rinovum Women's Health, Inc.

 
Title: TP-00002 Rinovum Subsidiary 2, LLC: Disposable Stress Urinary Incontinence Pessary 
Device Efficacy and Safety Study 
Protocol Identifying Number: <TBD>  
Principal Investigator: < Principal investigator>  
Sponsor: Rinovum Subsidiary 2, LLC. 
Funded by: Rinovum Subsidiary 2, LLC.  
Version Number: v3.0 2017 November 03  
 
 

References: 
• 
21 CFR Part 812 Investigational Device Exemptions 
• 
21 CFR Part 50 Protection of Human Subjects; Informed  
 
• 
21 CFR Part 54 Financial Disclosure by Clinical Investigators 
• 
21 CFR Part 56 Institutional Review Boards 
• 
45 CFR Part 46 Protection of Human Subjects 
• 
United States Food and Drug Administration (FDA), Medical Device Clinical Study Guidance  
• 
Guidance for Industry and Food and Drug Administration Staff: Clinical Investigations for the 
Treatment of Urinary Incontinence 
 
 
 
 
 

 
L I S T O F A B B R E V I A T I O N S                                                                                                                               
 
AE 
Adverse Event 
ANCOV
Analysis of Covariance 
CFR 
Code of Federal Regulations 
CIOMS 
Council for International Organizations of Medical Science 
CLIA 
Clinical Laboratory Improvement Amendments 
CMP 
Clinical Monitoring Plan 
CMS 
Centers for Medicare and Medicaid Services 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
DCC 
Data Coordinating Center 
DHHS 
Department of Health and Human Services 
DSMB 
Data Safety Monitoring Board 
eCRF 
Electronic Case Report Forms 
FDA 
Food and Drug Administration 
FDAAA 
Food and Drug Administration Amendments Act of 2007 
FFR 
Federal Financial Report 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practices 
GMP 
Good Manufacturing Practices 
GWAS 
Genome-Wide Association Studies 
HIPAA 
Health Insurance Portability and Accountability Act 
IB 
Investigator’s Brochure 
ICH 
International Conference on Harmonisation 
ICH E6 
International Conference on Harmonisation Guidance for Industry, Good Clinical 
Practice: Consolidated Guidance 
ICMJE 
International Committee of Medical Journal Editors 
IDE 
Investigational Device Exemption 
IND 
Investigational New Drug Application 
IRB 
Investigational Review Board 
ISO 
International Organization for Standardization 
LSMEA
Least-squares Means 
MedDR
Medical Dictionary for Regulatory Activities 
MCID 
Minimal Clinical Important Difference 
MOP 
Manual of Procedures 
MSDS 
Material Safety Data Sheet 
NIH 
National Institutes of Health 
NIH IC 
NIH Institute & Center 
OHRP 
Office for Human Research Protections 
OTC 
Over the Counter 
PI 
Principal Investigator 
QA 
Quality Assurance 
QC 
Quality Control 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SMC 
Safety Monitoring Committee 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
UP 
Unanticipated Problem 
US 
United States 
 
 
 

 
 
  S T A T E M E N T O F C O M P L I A NCE                                                                                                                   
 
This clinical trial 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 812) 
• 
ICH E6 
 
All key personnel (all individuals responsible for the design and conduct of this trial) have 
completed Human Subjects Protection Training.] 
 
 
I agree to ensure that all staff members involved in the conduct of this study are informed about 
their obligations in meeting the above commitments. 
 
Principal Investigator: Print/Type Name 
 
Signed:  Date: _________________________________________ 
 
 
 

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  P R O T O C O L S U M M A R Y  
Title: Rinovum Subsidiary 2, LLC. Disposable Stress Urinary Incontinence Device Efficacy and 
Safety Study 
Précis:   
This study is an interventional, single arm, multi-center study. It will be 
conducted at sites in the northeastern United States. The protocol will be 
approved by Chesapeake IRB or applicable local IRBs. The sample size will 
consist of approximately 50 participants. Participants will undergo an initial 
control period in which preweighed pads will be worn for 7 consecutive days 
for 12 hours. This will be followed by device usage for 14 consecutive days 
where participants will wear both device and preweighed pads 
simultaneously. for 12 hours.  
 
Objectives:  
The purpose of this study is to evaluate the efficacy and safety of an over-
the-counter (OTC) disposable stress urinary incontinence (SUI) pessary 
device. Specifically, this study will evaluate the effectiveness of the pessary 
device by assessing reduction in urine leakage in approximately 50 women 
with Stress Urinary Incontinence (SUI). Efficacy will be assessed by mean 
pad weight gain per hour, reduction of stress urinary incontinence events 
per day, and a quality of life questionnaire. The safety of the OTC SUI 
pessary device will be evaluated by assessing all adverse events, including 
the results of urinalysis, vaginal swab, and vaginal examination.  
 
Primary Objective: Demonstrate effectiveness of device usage  
Important Secondary Objectives: Device reduces episodes of incontinence, 
improves quality of life, and is safe for over-the-counter (OTC) use.  
Endpoints:  
Primary Endpoint: Mean pad weight gain reduction per hour is >50% during 
the last 7 days of the treatment phase as compared to the baseline phase. 
Important Secondary Endpoints: 
(1) Reduction in mean number of SUI episodes per day from the 7-day 
baseline period to the last 7 days of the 14-day device treatment period. 
Participants will record SUI episodes in the Study Diary during the 
baseline (7 days) and treatment (14 days) periods. Negative values are 
indicative of efficacious outcome. 
(2) Change in Quality of Life as Measured by the ICIQ-LUTSqol Quality of 
Life Questionnaire. 
The Quality of Life Questionnaire to be performed at baseline, before, 
and after treatment phase of the study is based on 20 questions referring 
to areas which may have been influenced or changed by accidental urine 
loss and/or prolapse. These questions are assigned a value of, 1 = 'Not 
at all,' 2= 'Slightly,' 3 = 'Moderately,' or 4 'A lot.' Each area is then 
assessed on a scale of 1-10 to see how much it bothers them. The 
Questionnaire is scored by taking the average score of items and then 
multiplying that value by 25 to put scores on a scale from 0 to 100. A 
lower score is considered less impact to quality of life and a higher score 
reflects more impact to quality of life. In the same manner, a reduction 
in scores from baseline reflects improved quality of life. A reduction in 

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score of > 3.7 is considered the Minimum Clinically Important Difference 
(MCID). 
(3) Evaluation of Adverse Event assessments to determine device is 
safe for use. 
Important Exploratory Endpoints: 
(1) Participants can successfully use the device in accordance with 
the given Instructions for Use.  
(2) Participants will find the device comfortable enough to 
demonstrate compliance with the study procedures during the 
device treatment phase. 
 
 
Population:   
Approximately 50 female participants over the age of 18 who have 
been physician diagnosed with Stress Urinary Incontinence; have a 
normal voiding history; are familiar with the use of tampons; and have 
had a Normal Pap Smear <36 months prior to study enrollment.  
 
Phase:  
Efficacy and Safety 
 
Number of Sites enrolling participants: 4 
 
Description of Study Agent:  A disposable stress urinary incontinence pessary device worn 
daily for 12 hours.  
 
Endpoint Classification:  
Efficacy and Safety Study 
Interventional Model:  
Single Group, Open Study 
Masking:  
Open Label 
Primary Purpose:  
Efficacy and Safety 
 
Study Duration:  
6-12 months 
 
Participant Duration:  2 months 
 
 
 
 

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  S C H E M A T I C O F S T U D Y D E S I G N                                                                                                               
 
Prior to Enrollment (Screening) 
 
 
 
 
 
 
 
 
 
 
 
 
Enrollment/Visit 1 Time Point 
 
 
 
 
 
 
 
 
 
 
 
 
 
Visit 2 Time Point 
 
 
 
 
 
 
 
 
 
 
 
Visit 3 Time Point 
 
 
 
 
 
 
 
 
Total N:  Complete a questionnaire by the physician. Participant will also complete a 
baseline Quality of Life Questionnaire. 
Participant will receive 14 preweighed pads to take home. Participant will perform 
control phase of study wearing pads for 12 hours/day for 7 consecutive days. Pads 
will be returned by participant for weighing and data collection. 
NOTE: Results of the laboratory tests from the screening visit (pregnancy test, 
vaginal examination and urinalysis test) may deem a participant ineligible for 
enrollment due to positive pregnancy result, positive vaginal infection requiring 
treatment, or positive urinary infection requiring treatment, respectively. 
 
Total N:  Obtain informed consent. Screen potential participants by inclusion and 
exclusion criteria; obtain and document medical history. Confirm that participant 
symptoms indicate SUI diagnosis. Perform the urine pregnancy test (if applicable), 
urinalysis, vaginal examination and symptom evaluation to ensure participant has 
no active urinary or vaginal infection requiring treatment. A vaginal swab will be 
performed to establish baseline vaginal microflora. Perform usability and fit 
assessment test.   
NOTE: Results of the SUI diagnosis assessment and fit assessment may deem 
participant ineligible for enrollment due to urge incontinence or mixed (stress and 
urge) incontinence diagnosis or poor /improper fit. To simulate OTC use, 
participants will be asked to perform self-selection and assess fit based on the 
product labeling prior to confirmation by the PI. 
Total N: Urine pregnancy test, if applicable, to rule out pregnancy, vaginal 
examination, and symptom evaluation will be repeated to rule out any potential 
infection requiring treatment. Vaginal swab will also be repeated to evaluate changes 
in vaginal microflora. Quality of Life questionnaire will be repeated. Participants will 
be given 20 study devices and 28 preweighed pads to perform the treatment phase of 
the study. Participants will wear 14 devices and 14 pads simultaneously for 14 
consecutive days. Pads will be returned by participant for weighing and data 
collection, and participants will record information regarding activity level and quality 
of life. 
Total N:  Examination to determine final safety evaluation via investigator vaginal 
examination, vaginal swab, urinalysis, study questionnaire to collect final comments 
on device usage, and repeat Quality of Life questionnaire to evaluate changes in 
quality of life post treatment with device  

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Note (1): For pre-menopausal women, and women who have not undergone a hysterectomy, a Urine 
Pregnancy Test, usually to be done within 24 hours prior to study intervention is required. Results must be 
available prior to administration of study product, unless otherwise indicated by the physician. 

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Sponsor 
 
 
Stephen Bollinger, President 
Rinovum Subsidiary 2, LLC. 
300 Oxford Drive Suite 330  
Monroeville, PA 15146 
412-200-7996 
sbollinger@rinovum.com 
Principal Investigator 
<Insert text> 
Sub Investigator 
<Insert text> 
Study Coordinator 
<Insert text> 
Clinical Laboratory 
<Insert text> 
Statistician:  
 
Peter Gaccione 
gaccione@hcp.med.harvard.edu 
  
 
 
 
 
 
Stress urinary incontinence (SUI) occurs predominantly among women. SUI is characterized by 
loss of urine resulting from increased abdominal pressures that occur when coughing, laughing, 
sneezing, running, lifting or walking. SUI causes quality of life degradation and contributes to 
women refraining from maintaining normal physical activities, and is also associated with low 
libido, vaginal dryness, dyspareunia. 
 
Currently, there are several types of treatment options for SUI such as: 
 
- 
Lifestyle/Behavioral changes including weight loss, pelvic floor strengthening exercises 
(Kegel), biofeedback, dietary changes and advisement to decrease fluid intake have been 
shown to have good results for motivated patients. However, it is difficult to compliance is 
relatively low. 
- 
Non-surgical treatments, including Absorbent Pads; Pessary support devices (originally 
intended to support bladder prolapse) which elevate the vesico-urethral angle, devices that 
provide urethral occlusion, and weighted cones. 
- 
Pharmacologic Therapy  
- 
Surgical methods, including retropubic urethropexies, suburethral slings and periurethral 
injection of bovine collagen or carbon-coated beads.1 
 
Relevant clinical research demonstrates a need for nonsurgical options for treating SUI. Since 
the aging populations is growing, there are more instances of incontinence. Conservative 
treatment is fundamental as it is the only type of care many patients need or can undergo.2  
                                                          
1Mark Deutchman, Meghan Wulster-Radcliffe. Stress Urinary Incontinence in Women: Diagnosis and Medical 
Management, 2005. 
2 Metcalf, et al. The Non-surgical Options for SUI – Is Any One Optimal?, 2016 
1            KEY  ROLES 
2            INTRODUCTION:  BACKGROUND  INFORMATION  AND  SCIENTIFIC  RATIONALE 
2.1        BACKGROUND  INFORMATION 

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Approximately 25% of premenopausal and 40% of postmenopausal women suffer from urinary 
incontinence, with the peak incidence beginning at around age 45-49. Of those dealing with 
urinary incontinence, 51% have stress urinary incontinence. Women that are Caucasian, have a 
BMI > 30 kg/m2, have been pregnant, and have had a vaginal delivery are at a higher risk of 
developing SUI. Intrinsic factors contributing to development of SUI include urethral musculature, 
blood flow and innervation. Extrinsic factors include degree of urethral support, patient weight, 
and degree of physical activity. 
 
Multiple treatment methods have been studied, including surgery, pharmacological treatments, 
physical/behavioral therapy, and non-surgical options such as pessaries and intravaginal 
devices. While multiple treatment options exist, less than a third of women seek intervention in 
the first 12 months of experiencing SUI symptoms.  
 
Surgical interventions have existed for over 100 years and are regarded as the most effective and 
durable treatment option for urinary incontinence; however, this surgery comes with physiological 
risks to the patient, high hospital costs, and productivity loss during recovery. While 
pharmacological options exist, they are not the standard of care in urinary incontinence treatment 
in the United States. While some topical pharmacologic are proven to resolve incontinence in some 
women, studies have shown both adrenergic drugs and oral hormonal treatments ineffective. One 
study revealed an 80% increase in incontinence in post-menopausal women. Not only have 
studies shown pharmacological treatments ineffective, they also carry side effects such as nausea, 
dry mouth, and fatigue. Having nonsurgical treatments are vital so that patients have reversible, 
safer, and less costly options to try before resorting to surgical and pharmacological treatments. 
 
The primary nonsurgical and nonpharmacological options include behavioral and physical therapy, 
pessaries, and disposable, intravaginal devices, which are all relatively low risk and low cost. 
Pelvic floor muscle training combined with bladder training is effective; however, it is difficult for 
patients to comply with this treatment regimen and requires more extensive physician guidance. 
Understanding predictors of success will aid in patient counseling on treatment options. 
Menopausal status, education level, UI surgery status, and incontinence frequency were 
consistently identified as predictors of success across those that used behavioral therapy, 
pessaries, and a combination of both. Women that were post-menopausal, had higher education, 
no previous UI surgery, and had low incontinence frequency were found to have the most success 
when using nonsurgical treatments. 
 
A study comparing cost utility of different treatment options revealed that incontinence pessaries 
were the most cost effective. Pessaries have been found to increase continence by 64-75%. 
While 50-75% of women decline pessaries when recommended, over three quarters of patients 
that use the pessary continue to use after one year. Studies have also revealed that women do 
not perceive any difference in the effectiveness of pessary treatment versus physical therapy 
treatment; however, pessary use is also associated with pain, irritation, UTIs and difficulty in 
physician fitting of the pessary.  
 
A study performed to evaluate the efficacy and safety of a novel disposable intravaginal device 
for the treatment of SUI was performed at 2 sites in Israel. Sixty women were recruited and 
enrolled into the study and used the device for 28 – days after a 7-day control period. During the 
control period, preweighed pads were worn daily for 8 hours to determine a baseline for 
participants. This period was followed by a 28-day usage period. The last 14 days of the control 
period were used to allow for participants to find the right size device. The primary endpoint was 

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the percentage of women who achieved a > 70% reduction in pad weight gain (PWG) from the 
control period to the last 14 days of device usage. The results demonstrated that 85% of 
participants met the success criteria. The device was concluded to be easy to use, well-tolerated, 
and effective in reducing SUI3. 
 
As is recommended in the Guidance for Industry and FDA Staff:  Clinical Investigations of 
Devices Indicated for the Treatment of Urinary Incontinence, the Rinovum Subsidiary 2, LLC. 
SUI Device Pivotal Study will include the use of a voiding diary to document leakage occurrence 
daily. Also, as recommended in the guidance, the study will use pad-weighing to monitor efficacy 
of the device. The 24-hour test parameter will be used, but will be tailored to be in line with the 
amount of time the device will be used for treatment each day (12 hours). Participants will be 
provided with ziplock bags and mailers so that used pads can be collected daily and weighed by 
the site clinical team within 48 hours to determine the amount of pad weight gain (PWG). Note 
that more than 1 pad may be worn throughout each day depending on the amount of leakage 
protection required. 
 
 
 
This study is an interventional, open label, single-arm, clinical study in which participants will 
serve as their own controls. This study will enroll participants deemed eligible per the 
Inclusion/Exclusion Criteria. This study will evaluate the safety and effectiveness of the Rinovum 
Subsidiary 2 (RS-2) SUI pessary device by assessing reduction in urine leakage in 
approximately 50 women with SUI. Efficacy will be assessed by reduction in pad weight gain, 
frequency of stress urinary incontinence events, and a quality of life questionnaire. The study 
design consists of a control/no treatment period for each subject and a device treatment period 
for each subject.  
 
The participants in this study will use the pre-weighed pads daily for 12 hours per day to obtain 
baseline control urine leakage data. This baseline will be for 7 consecutive days. The pads may 
be changed as necessary during this time. The same participants will use the device, and the 
same pre-weighed pad method for 14 consecutive days during the treatment period. Participants 
will be asked to schedule the treatment phase during a time when they will not have an 
interruption in the treatment phase such as menstrual cycle or travel. Patients will be asked to 
perform the treatment period within 21 days. In both the non-treatment and treatment phase of 
the study, the preweighed pads will be collected and weighed for use in calculating pad weight 
gain (PWG). 
 
Safety analysis will include results of urinalysis, vaginal swab, vaginal examination, and 
evaluation of adverse events.  
 
Usability of the device will be assessed by the PI at Enrollment where the participant will insert 
the device while following the Instructions for Use.  The PI will examine the device inside the 
vagina to ensure successful placement and fit. 
 
 
 
The risk profile of the Rinovum Subsidiary 2 SUI device is considered to be low. Risks to 
participants in this study are comparable to those routinely encountered with using vaginal 
                                                          
3 Ziv E, Stanton SL, Abarbenel J. Efficacy and safety of a novel disposable intravaginal device for treating stress 
urinary incontinence. Am J Obstet Gynocol 2008; 198:594.e1 – 594.e7. 
2.2        RATIONALE 
2.3        POTENTIAL  RISKS  AND  BENEFITS 

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pessaries.  The study presents no more than minimal risk of harm to participants and involves no 
procedures for which written consent is normally required outside of the research context with a 
Class II device.  
 
Potential risks include the following short-term risks: 
• Sensitivity to the materials used in the device; however, the probability is low due to the 
design specification. 
• Injury if the user does not understand the instructions for use. Prior to the pivotal study, 
label comprehension and simulated use testing will occur to refine the labelling and 
demonstrate safety to proceed with the pivotal study 
• Irritation to the vaginal area 
• Vaginal bleeding/spotting 
• Urinary Tract Infection (UTI) 
• Vaginal infection 
• Urine Retention 
• Infection if the device is not used as indicated. For example, reuse of the device could 
put the user at risk of infection. Instructions for use will include details regarding single, 
disposable use of the device and the specifications will preclude reuse by design. 
• Confidentiality 
 
There are no known long-term risks associated with this study. 
 
This study is a non-significant risk study. The device is not intended as an implant or for use in 
supporting or sustaining human life. The device is intended to treat by assisting with 
management of the symptoms associated with a disease (Stress Urinary Incontinence). Due to 
the low risk profile associated with the Rinovum Subsidiary 2 SUI device, as well as other similar 
devices, it does not present serious risk to the health, safety, or welfare of a subject.  
 
The materials used in the manufacturing of this device are medical-grade. During the screening 
process, a pregnancy test, vaginal examination and urinalysis will be performed to rule out a 
pregnancy, vaginal infection, or UTI, respectively. The device will be tested the screening visit to 
ensure fit, comfort and ability to urinate while wearing the device.  A vaginal swab will be collected 
to establish baseline vaginal microflora, but will not be used for determining eligibility to enroll. 
Participants’ most recent Pap smear within 36 months must be normal.  Each of the participants 
will receive an identification number during enrollment. This number will be the only identifying 
factor on the CRF/questionnaire.  The PI will maintain the participant information in a secure 
location.  The Sponsor shall have access to the study data after it has been de-identified to analyze 
the data to determine success of the study. 
 
Each of the devices used in this study will be labeled “Caution: Investigational device.  Limited by 
United States law to investigational use”.  Additionally, each device will have a specific lot number.   
 
Patient’s undergoing successful intravaginal pessary treatment for SUI have been shown to have 
improvement in quality of life, so long as the device is being used. The quality of life improvement 
seen in patients undergoing successful SUI treatment include physical mitigation of symptoms 
which result in potential social effects, psychological effects and decrease in activity. 
 
Non-surgical treatment options are important to the subject population. SUI device interventions 
that demonstrate efficacy and safety could significantly improve the quality of life for a condition 
that most patients do not like to discuss, even with their physicians. Surgical options are typically 
used as a last resort, so the RS-2 SUI pessary device could provide a bridge to surgery option for 

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patients. For this reason, the potential benefits associated with this study outweigh the risks 
involved. 
 
The potential benefits to participants during this study include increased quality of life, increased 
social activity (including exercise), psychological improvement, and increased confidence due to 
decreased urinary leakage.  
   
 
 
This study is an interventional, open label, clinical study. The purpose of this study is to evaluate 
the efficacy and safety of the Rinovum Subsidiary 2, LLC disposable SUI pessary device. 
Specifically, this study will evaluate the effectiveness of the pessary device by assessing 
reduction in urine leakage in approximately 50 women with Stress Urinary Incontinence (SUI). 
Efficacy will be assessed by the reduction in mean pad weight gain per hour, reduction in the 
mean number of stress urinary incontinence events per day, and a quality of life questionnaire. 
Primary Objective is to demonstrate effectiveness of device usage. Important Secondary 
Objectives include demonstrating that the device reduces episodes of incontinence, improves 
quality of life, and is safe for over-the-counter (OTC) use. The safety will be evaluated by 
assessing all adverse events, including the results of urinalysis, vaginal swab, and vaginal 
examination. 
 
 
 
 
 
60 to 70 women having diagnosed stress urinary incontinence (SUI) will be recruited from 
multiple study sites and the general population, while approximately 50 women will be included 
in the Per Protocol population. The participants will wear preweighed pads for 7 consecutive 
days during the non-treatment (control) phase. Participants will then use the device for 14 
consecutive days during the treatment phase. During enrollment, before treatment phase and 
after treatment phase, a vaginal swab will be collected to determine any changes in the vaginal 
microflora of the participant.  
 
Intent to Treat Population (ITT): Any subject enrolled who gets a pre-weighed pad for the control phase.  
This is expected to be 60-70 subjects.  
 
Modified Intent to Treat Population (mITT): Any subject enrolled who gets through the control phase, is 
given the device and pads for the treatment period, and who uses the device such that there is at least 
one data point to analyze - i.e., use of the pad for at least one hour during the last 7 days of the treatment 
period.  A subject who is not in the study at the beginning of the last 7 days of the treatment period is in 
the ITT population but not the mITT population.  The mITT is the population the analysis will be done on. 
 
Per Protocol Population (PP):  Any subject getting through the entire treatment period and has 
complete data (i.e., pad weight reduction data for the last 7 days of the treatment period).  For example, 
someone having only data for 6 out of the last 7 days of the treatment period is in the mITT population but 
not the PP population. 
 
Safety Population (SP):  Same as ITT. 
 
 
3            OBJECTIVES  AND  PURPOSE 
4            STUDY  DESIGN  AND  ENDPOINTS 
4.1        DESCRIPTION  OF  THE  STUDY  DESIGN 
4.2        ANALYSIS POPULATIONS 
4.3       STUDY  ENDPOINTS 

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The primary endpoint is the percentage reduction in mean pad weight gain per hour of >50% 
during the 14-day treatment phase versus the 7-day baseline phase. The PWG percentage 
reduction will be calculated by comparing the mean PWG over the 7-day baseline non-treatment 
phase with the last 7 days of the 14-day treatment phase for each individual participant.   
 
Important secondary endpoints will be measured based on anecdotal evidence or feedback from 
the subjects. These secondary endpoints are as follows: 
(1) Reduction in mean number of SUI episodes per day from episodes from the 7-day 
baseline period to the last 7 days of the 14-day device treatment period as measured 
as reduction (improvement) in stress urinary incontinence episodes. Participants will 
record SUI episodes in the Study Diary during the baseline (7 days) and treatment (14 
days). Negative values are indicative of efficacious outcome. 
(2) Change in Quality of Life as Measured by the ICIQ-LUTSqol Quality of Life 
Questionnaire. 
The Quality of Life Questionnaire to be performed at baseline, before and after treatment 
phase of the study is based on 20 questions referring to areas which may have been 
influenced or changed by accidental urine loss and/or prolapse. These questions are 
assigned a value of, 1 = 'Not at all,' 2= 'Slightly,' 3 = 'Moderately,' or 4 'A lot.' Each area 
of changed is then assessed on a scale of 1-10 to see how much it bothers them. The 
Questionnaire is scored by taking the average score of items and then multiplying the 
average by 25 to put scores on a scale from 0 to 100. A lower score is considered less 
impact to quality of life and a higher score reflects more impact to quality of life. In the 
same manner, a reduction in scores from baseline reflects improved quality of life. A 
reduction on score of > 3.7 is considered the Minimum Clinically Important Difference. 
(3) Evaluation of Adverse Event assessments to determine device is safe for use. 
Important Exploratory Endpoints are as follows: 
(1) Participants can successfully use the device in accordance with the given Instructions 
for Use.  
(2) Participants will find the device comfortable enough to demonstrate compliance with 
the study procedures during the device treatment phase. 
 
 
 
 
 
 
Inclusion Criteria: To be eligible to participate in this study, an individual must meet all of the 
following criteria: 
 
• 
Provision of signed and dated informed consent form 
• 
Literacy must be in English (able to read and understand Informed Consent) 
• 
Stated willingness to comply with all study procedures and availability for the duration 
of the study 
• 
Female, aged >18 
5            STUDY  ENROLLMENT  AND  WITHDRAWAL 
5.1        PARTICIPANT  INCLUSION  CRITERIA 

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• 
Be in generally good heath as determined by the Investigator 
• 
Have a physician diagnosis of SUI that occurred prior to or during the screening visit of 
this study 
• 
Have a > 3-month history of experiencing > 3 episodes of SUI per week 
• 
Be willing to use the investigational pessary device for the control of urinary 
incontinence 
• 
Have experience with wearing a tampon 
• 
Have normal PAP smear results within the last 36 months, if applicable. 
 
 
 
Exclusion Criteria: An individual who meets any of the following criteria will be excluded from 
participation in this study: 
 
• 
Is pregnant, or planning to become pregnant during the study 
• 
Has been physician diagnosed with urge urinary incontinence or mixed urinary 
incontinence prior to or during the screening visit for this study 
• 
Is post-partum within 3 months 
• 
Has had an intrauterine device (IUD) placement of less than 6 months 
• 
Has self-reported difficulty emptying her bladder; 
• 
Has a history of Toxic Shock Syndrome (TSS) or symptoms consistent with TSS; 
• 
Has experienced difficulty inserting or wearing an intra-vaginal device, including a 
tampon; 
• 
Has had vaginal surgery, perineal surgery, uterine surgery, or abortion (spontaneous or 
induced) within the past 3 months; 
• 
Has any Screening laboratory value outside the laboratory reference range considered 
clinically significant by the Investigator which could impact the safety of the participant 
or the outcome of the study 
• 
Has an active urinary tract infection or vaginal infection requiring treatment 
• 
If for any reason, the Investigator decides that the participant should not participate in 
the study. 
• 
Class III Obesity (BMI> 40.0 kg/m2) 
• 
Advanced prolapse 
• 
Fit assessment is not successful during screening visit 
 
 
5.2        PARTICIPANT  EXCLUSION  CRITERIA 

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Study participants will be recruited with the use of an advertisement flyer to be posted locally and 
online. They will also be recruited by the primary investigators patient pool and general public.  
Any interested potential participants will contact the Primary Investigator or Study Coordinator.  
The participants will be informed that participation is voluntary and the decision to participate or 
not, will in no way affect their future care. Subsequently, the participants will be given a complete 
and thorough explanation of the benefits and risks or discomforts that may be anticipated with 
this study. 
 
Participants will be given a monetary compensation for time and transportation in the 
amount of $550. 
In addition: 
• 
The target sample size is approximately 50 participants. An anticipated number 
of 60-80 patients will be screened to reach the target enrollment. 
• 
Multiple sites will be used to recruit participants to be enrolled from the U.S. 
• 
Source of participants will come from the primary investigators patient pools as well 
as the general public. 
• 
Recruitment venues will include advertisement/flyer posting 
• 
Advertisements will include local flyers 
 
 
 
Participants are free to withdraw from participation in the study at any time upon 
request. An investigator may terminate participation in the study if: 
 
• 
Any clinical adverse event (AE), laboratory abnormality, or other medical condition or 
situation occurs such that continued participation in the study would not be in the 
best interest of the participant 
• 
The participant meets an exclusion criterion (either newly developed or not 
previously recognized) that precludes further study participation.] 
 
Data for patients lost to follow up/withdrawal will be collected if possible. Subjects in the ITT 
population but not in the mITT group will be represented in all tables except those for the primary 
and secondary endpoint analysis. Data from those withdrawing from or lost to follow-up in the 
mITT population will be used for the primary endpoint and, if there is at least one full day’s worth 
of data on the number of SUI episodes available, then this subject will also be included in the 
analysis of change in number of SUI episodes. Attempts will be made to contact subjects 
withdrawing from or lost to follow-up to the mITT population to administer the QoL questionnaire. 
If successful these subjects will be included in the change in QoL analysis. For mITT subjects not 
completing the treatment phase, a “last observation carried forward” approach will be used (see 
section 10 “Statistical Considerations”). If it appears that there will not be 50 subjects in the PP 
population further recruitment and enrollment will be necessary. 
 
 
 
 
This study may be temporarily suspended or prematurely terminated if there is sufficient 
reasonable cause. Written notification, documenting the reason for study suspension or 
5.3        STRATEGIES  FOR  RECRUITMENT  AND  RETENTION 
5.4        PARTICIPANT WITHDRAWAL OR TERMINATION 
5.5        PREMATURE  TERMINATION  OR  SUSPENSION  OF  STUDY 

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termination, will be provided by the suspending or terminating party to <investigator, funding 
agency, the IND/IDE sponsor and regulatory authorities>. If the study is prematurely 
terminated or suspended, the PI will promptly inform the IRB and will provide the reason(s) 
for the termination or suspension. 
 
Since this study is a non-significant risk study, there are no stopping rules required. 
 
Circumstances that may warrant termination or suspension include, but are not limited to: 
• 
Determination of unexpected, significant, or unacceptable risk to participants 
• 
Insufficient compliance to protocol requirements 
 
Study may resume once concerns about safety, protocol compliance, and data quality are 
addressed and satisfy the sponsor, IRB and FDA. 
 
 
 
 
The study devices will be provided by the sponsor and delivered to the investigator. Device 
accountability and distribution records will be maintained. The product will be packaged to 
prevent contamination. The PI will be trained by Rinovum Subsidiary 2, LLC. personnel on 
device placement for the screening visit fit assessment. Participants will not be trained on how 
to use the device since the indications for use are OTC. They will be given the IFU and 
instructed to demonstrate insertion and removal under physician supervision to verify that they 
successfully completed the steps. The fit assessment will include participant input to 
demonstrate proper understanding of whether or not the device is appropriate for her. 
The manufacturer of the device is Rinovum Subsidiary 2, LLC. Design Controls and Good 
Manufacturing Procedures shall be used in the manufacturing of the device, in accordance with 
21 CFR part 820. The PI will give the participants 42 preweighed pads for the duration of the 
study. The PI will give participants 20 SUI devices. Participants will complete the baseline first 
wearing only preweighed pads and then complete the treatment phase, where participants will 
wear both a preweighed pad and an SUI device.  
 
The SUI devices consist of the following: 
• 
Device size(s): One size (Quantity: 20) 
• 
Device model(s): SUI Pessary Device, Disposable, Single Use  
• 
Preweighed pads will be provided to the participant (quantity: approximately 42) 
• 
Duration of Use: The device will be used for a period of 12 hours 
• 
Frequency of use: 14 consecutive days  
• 
Double ziplock bags and shippers for mailing used pads to the study site for 
weighing 
 
The storage and shelf life requirements for the Rinovum Subsidiary 2, LLC SUI Pessary device 
are as follows: 
The device is made of plastic-like and silicone-like materials. These materials have a long 
history of use and have been shown not to deteriorate over time. 
 
 
6            STUDY  AGENT 
6.1        STUDY  AGENT(S)  AND  CONTROL  DESCRIPTION 
6.2        STUDY  AGENT  ACCOUNTABILITY  PROCEDURES 

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A Device Accountability Form shall be used to document the following: 
• 
Reconciliation of investigational device accountability; 
• 
Verify that the device accountability documentation is accurate and complete; 
• 
Arrange for return of all unused devices and clinical supplies to Rinovum Subsidiary 2, 
LLC. as applicable. 
 
 
This study will include the following procedures: 
• 
Medical history 
• 
Fit assessment to ensure that device is a proper fit and does not prevent voluntary 
voiding 
• 
Physical examination (vital signs, height, weight, vaginal exam for vaginal infection 
evaluation) 
• 
Vaginal swab to evaluate vaginal microflora 
• 
Urinalysis to check for active urinary infection 
• 
Urine Pregnancy Test (if applicable) 
• 
Participants will be given an IFU and demonstrate insertion and removal of device under 
physician supervision 
• 
Distribution of preweighed pads for the baseline phase 
• 
Distribution of preweighed pads and devices for the treatment phase 
• 
Return via mail all worn pads for weight recording 
• 
Collection of study diaries, to be completed at home by the participant 
• 
Quality of Life Questionnaire  
 
 
A urine pregnancy test, if applicable, will be performed no more than 24 hours prior to study 
intervention. A urinalysis will be performed to ensure no infections are active at the time of 
screening and at the end of treatment phase. Results of both urine pregnancy test and urinalysis 
test shall be made available prior to administration of study product. 
 
A vaginal swab shall be obtained at the time of enrollment, before treatment phase, and after 
end of treatment phase to evaluate any changes in vaginal microflora.
 
Prior to enrollment, screening questions, a medical file review, a physical examination, 
pregnancy test (if applicable), urinalysis, and a human factors and a fit assessment will be used 
to determine/assess whether a participant meets the eligibility criteria. A vaginal swab shall be 
performed to establish baseline vaginal microflora. These activities must be performed within 1 
week of enrollment. Informed consent will be obtained prior to any screening procedures. The 
human factors and fit assessment will include the following: 
• 
Participant will perform self-insertion and removal in accordance with the IFU under  
supervision of physician 
• 
Participant will provide feedback regarding the fit of the device based on the IFU 
description of proper fit without input of the physician 
• 
Physician will verify device is a proper fit for participant after participant performs self-
insertion (if  physician determines the device is not a good fit for the participant, the 
participant may be terminated from the study) 
 
7            STUDY  PROCEDURES  AND  SCHEDULE 
7.2        LABORATORY  PROCEDURES/EVALUATIONS 
7.3        STUDY  SCHEDULE 

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Enrollment/Visit #1 schedule shall consist of the following: 
• 
Provide participants with a description of what to expect with the study 
• 
Participant will complete a Quality of Life Survey 
• 
Provide the patient with a Baseline Study Diary for them to keep track of their leaking 
patterns for the first phase of the study 
• 
Physician will administer 14 preweighed pads for the patient to wear for 7 consecutive 
days.   
• 
Record any adverse events 
 
NOTE: all worn pads will be placed in preweighed, double sealed, ziplock bags and returned 
to the clinical site via mail within 48 hours of use by the participant for weighing throughout 
the entirety of the study 
 
NOTE: to minimize time between pad wearing and pad weighing, participants will be mailing 
back all worn pads immediately upon completion of the 7-day wear to the site. The site will 
record the pad weights in the Pad Weight Log form. 
 
Visit #2 schedule shall consist of the following: 
• 
Update Medical History, if applicable 
• 
Perform a urine pregnancy test, if applicable 
• 
Perform a vaginal swab for vaginal microflora assessment 
• 
Assess for any symptoms of active vaginal infections requiring treatment (if a patient is 
symptomatic of a vaginal infection, they may be treated and enrolled at a later date once 
vaginal infection has resolved). 
• 
Collect Baseline Study Diary from participant 
• 
Go over a series of questions with participants 
• 
Repeat the Quality of Life questionnaire 
• 
Administer the Treatment Study Diary 
• 
Physician will administer 20 devices and 28 preweighed pads to wear both device and 
pad simultaneously for 14 consecutive days. 
• 
Record any adverse events 
 
NOTE: to minimize time between pad wearing and pad weighing, participants will be mailing 
back all worn pads immediately upon completion of every 7-day wear to the site. The site 
will record the pad weights in the Pad Weigh Log form. If the participant returns for Visit #3 
within 2 days of completing the 14-day wear, they may bring the remaining 7 worn pads to 
the visit in lieu of mailing in pads at the physician’s discretion.  
 
Visit #3 schedule shall consist of the following: 
• 
Update Medical History, if applicable 
• 
Perform a urinalysis and vaginal microflora swab 
• 
Assess for any active vaginal infection 
• 
Collect and review the Treatment Study Diary 
• 
Collect and way any remaining worn pads, if applicable 
• 
Complete the Final Questionnaire 
• 
Complete the post-treatment Quality of Life Survey 
• 
Record any adverse events 

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Procedures 
 
Screening 
Enrollment/ 
Baseline 
(Visit 1)1 
Follow-Up 
(Visit 2) 
Follow-Up 
(Visit 3) 
Informed consent 
X 
 
 
 
Demographics 
X 
 
 
 
Medical history 
X 
X 
X 
X 
Physical exam 
X 
 
 
X 
Vital signs 
X 
X 
X 
X 
Height 
X 
 
 
X 
Weight 
X 
 
 
X 
Human Factors and Fit Assessment 
X 
 
 
 
Urine Pregnancy Test (if applicable) 
X 
 
X 
 
Urinalysis 
X 
 
 
X 
Administer Investigational Product 
 
 
X 
 
Adverse event evaluation 
 
X 
X 
X 
Vaginal swab 
X 
 
X 
X 
Questionnaire 
X 
X 
X 
X 
Quality of Life Survey 
 
X 
X 
X 
 
(1) Enrollment must be take place within 1 week of screening. Otherwise, screening procedures 
must be repeated prior to enrollment 
 
 
Prescription medications taken during study participation will be recorded on the case report 
forms (CRFs). For this protocol, a prescription medication is defined as a medication that can be 
prescribed only by a properly authorized/licensed clinician. Medications to be reported in the 
CRF are concomitant prescription medications, over-the-counter medications and non-
prescription medications. This information shall be collected during the medical history 
collection. There are no known concomitant medications for the treatment of SUI. However, 
concomitant treatments include pelvic floor strengtheners, such as Apex, biofeedback 
treatments, and physical therapy for SUI. 
 
 
 
There are no drug or food interactions for this study. Participants should not use the device while 
using a tampon, diaphragm, or other vaginal device. 
 
7.4        CONCOMITANT  MEDICATIONS,  TREATMENTS,  AND  PROCEDURES 
7.5        JUSTIFICATION  FOR  SENSITIVE  PROCEDURES 

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Not applicable. 
 
 
Not applicable. 
 
 
Participants will not have continued access to the study agent at study closure. 
 
 
  8 .1 S P E C I F I C A T I O N O F S A F E T Y P A R A M E T E R S                                                                                
 
An adverse event means any untoward medical occurrence associated with the use of an 
intervention in humans, whether considered intervention-related (21 CFR 312.32 (a)).] 
 
A Serious adverse event (SAE) is defined as an AE or suspected adverse reaction is 
considered "serious" if, in the view of either the investigator or sponsor, it results in any of the 
following outcomes: death, a life-threatening adverse event, inpatient hospitalization or 
prolongation of existing hospitalization, a persistent or significant incapacity or substantial 
disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical judgment, 
they may jeopardize the patient or participant and may require medical or surgical intervention 
to prevent one of the outcomes listed in this definition. 
 
An unanticipated adverse device effect (UADE) is defined any serious adverse effect on health 
or safety or any life-threatening problem or death caused by, or associated with, a device, if that 
effect, problem, or death was not previously identified in nature, severity, or degree of incidence 
in the investigational plan or application (including a supplementary plan or application), or any 
other unanticipated serious problem associated with a device that relates to the rights, safety, 
or welfare of participants (21 CFR 812.3(s)). 
 
  8 .2 C L A S S I F I C A T I O N O F A N A D V E R S E E V E N T                                                                                  
All AEs will be assessed by the PI using a protocol defined grading system. Describe the 
method of grading an AE for severity. For example, many toxicity tables are available for use 
and are adaptable to various study designs.  
 
The following guidelines will be used to describe severity. 
 
• 
Mild – Events require minimal or no treatment and do not interfere with the 
participant’s daily activities. 
• 
Moderate – Events result in a low level of inconvenience or concern with the 
therapeutic measures. Moderate events may cause some interference with 
functioning. 
• 
Severe – Events interrupt a participant’s usual daily activity and may require 
systemic drug therapy or other treatment. Severe events are usually potentially 
life-threatening or incapacitating. 
 
7.6        PROPHYLACTIC  MEDICATIONS,  TREATMENTS,  AND  PROCEDURES 
7.7        RESCUE  MEDICATIONS,  TREATMENTS,  AND  PROCEDURES 
7.8        PARTICIPANT  ACCESS  TO  STUDY  AGENT  AT  STUDY  CLOSURE 
8            ASSESSMENT  OF  SAFETY 

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The PI’s assessment of an AE's relationship to study device is part of the documentation 
process, but it is not a factor in determining what is or is not reported in the study. If there is 
any doubt as to whether a clinical observation is an AE, the event should be reported. All AEs 
must have their relationship to study agent assessed. In a clinical trial, the study product must 
always be suspect. To help assess, the following guidelines are used. 
 
• 
Related – The AE is known to occur with the study agent, there is a reasonable 
possibility that the study agent caused the AE, or there is a temporal relationship 
between the study agent and event. Reasonable possibility means that there is 
evidence to suggest a causal relationship between the study agent and the AE. 
• 
Not Related – There is not a reasonable possibility that the administration of the 
study agent caused the event, there is no temporal relationship between the study 
agent and event onset, or an alternate etiology has been established. 
 
The PI will be responsible for determining whether an AE is expected or unexpected. An AE 
will be considered unexpected if the nature, severity, or frequency of the event is not 
consistent with the risk information previously described for the study agent. 
 
The PI will record all reportable events with start dates occurring any time after informed 
consent is obtained until 7 (for non-serious AEs) or 30 days (for SAEs) after the last day of 
study participation. At each study visit, the investigator will inquire about the occurrence of 
AE/SAEs since the last visit. Events will be followed for outcome information until resolution or 
stabilization. 
  8 .3 T I M E P E R I O D A N D F R E Q U E N C Y F O R E V E N T A S S E S S M E N T A N D F O L L 
O W - UP                        
The occurrence of an AE or SAE may come to the attention of study personnel during 
study visits and interviews of a study participant presenting for medical care, or upon 
review by a study monitor. 
All AEs including local and systemic reactions not meeting the criteria for SAEs will be 
captured on the appropriate CRF. Information to be collected includes event description, time 
of onset, clinician’s assessment of severity, relationship to study product (assessed only by 
those with the training and authority to make a diagnosis), and time of resolution/stabilization 
of the event. All AEs occurring while on study must be documented appropriately regardless 
of relationship. All AEs will be followed to adequate resolution. 
Any medical condition that is present at the time that the participant is screened will be 
considered as baseline and not reported as an AE. However, if the study participant’s 
condition deteriorates at any time during the study, it will be recorded as an AE. UPs will be 
recorded in the data collection system throughout the study. 
Changes in the severity of an AE will be documented to allow an assessment of the duration 
of the event at each level of severity to be performed. AEs characterized as intermittent 
require documentation of onset and duration of each episode. 
The PI will record all reportable events with start dates occurring any time after informed consent 
is obtained until 7 (for non-serious AEs) or 30 days (for SAEs) after the last day of study 
participation. At each study visit, the investigator will inquire about the occurrence of AE/SAEs 
since the last visit. Events will be followed for outcome information until resolution or stabilization. 
 
  8 .4 R E P O R T I N G P R O C E D U R E S                                                                                                                
The study clinician will complete a SAE Form within the following timelines: 
• 
All deaths and immediately life-threatening events, whether related or unrelated, 
will be recorded on the SAE Form and submitted to the DCC/study sponsor 

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within 24 hours of site awareness. See Section 1, Key Roles for contact 
information. 
• 
Other SAEs regardless of relationship, will be submitted to the study sponsor 
within 72 hours of site awareness. 
 
All SAEs will be followed until satisfactory resolution or until the site investigator deems the 
event to be chronic or the adherence to be stable. Other supporting documentation of the event 
may be requested by the study sponsor and should be provided as soon as possible. 
The study sponsor will be responsible for notifying FDA of any unexpected fatal or life-
threatening suspected adverse reaction as soon as possible but in no case later than 7 
calendar days after the sponsor's initial receipt of the information. 
 
  8 .5 S T U D Y H A L T I N G R U L E S                                                                                                                       
The occurrence of an AE or SAE may come to the attention of study personnel during 
study visits and interviews of a study participant presenting for medical care, or upon 
review by a study monitor. 
 
All AEs including local and systemic reactions not meeting the criteria for SAEs will be 
captured on the appropriate CRF. Information to be collected includes event description, time 
of onset, clinician’s assessment of severity, relationship to study product (assessed only by 
those with the training and authority to make a diagnosis), and time of resolution/stabilization 
of the event. All AEs occurring while on study must be documented appropriately regardless 
of relationship. All AEs will be followed to adequate resolution. 
Any medical condition that is present at the time that the participant is screened will be 
considered as baseline and not reported as an AE. However, if the study participant’s 
condition deteriorates at any time during the study, it will be recorded as an AE. UPs will be 
recorded in the data collection system throughout the study. 
 
Changes in the severity of an AE will be documented to allow an assessment of the duration 
of the event at each level of severity to be performed. AEs characterized as intermittent 
require documentation of onset and duration of each episode. 
 
The PI will record all reportable events with start dates occurring any time after informed consent 
is obtained until 7 (for non-serious AEs) or 30 days (for SAEs) after the last day of study 
participation. At each study visit, the investigator will inquire about the occurrence of AE/SAEs 
since the last visit. Events will be followed for outcome information until resolution or 
stabilization. 
The study does not contain specific halting rules; however, the PI and monitor may halt the study 
due to AE/SAE analysis.   
8 .6 S A F E T Y O V E R S I G H T                                                                                                                              
Safety oversight will be under the direction of a clinical monitor with the appropriate expertise, 
including. The monitor and the sponsor will assess efficacy and safety data.  
 
 
Clinical site monitoring shall be conducted to ensure that the rights and well-being of human 
participants are protected, that the reported trial data are accurate, complete, and verifiable, and 
that the conduct of the trial is in compliance with the currently approved protocol/amendment(s), 
with GCP, and with applicable regulatory requirement(s). Monitoring for this study will be 
performed by a sponsor representative. Details of clinical site monitoring are documented in a 
CMP. The CMP describes in detail who will conduct the monitoring, at what frequency monitoring 
will be done, at what level of detail monitoring will be performed, and the distribution of monitoring 
9            CLINICAL MONITORING 

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reports. Monitoring Plans may vary slightly for each study site due to each study agreement. 
Independent audits will be conducted to ensure clinical practices are performed consistently 
across all participating sites.  
 
 
 
1 0 . 1   
P o p u l a t i o n s  
 
Intent to Treat Population (ITT): Any subject enrolled who gets a pre-weighed pad for the 
control phase.  This is expected to be 60-70 subjects.  
 
Modified Intent to Treat Population (mITT): Any subject enrolled who gets through the control 
phase, is given the device and pads for the treatment period, and who uses the device such that 
there is at least one data point to analyze - i.e., use of the pad for at least one hour during the 
last 7 days of the treatment period.  A subject who is not in the study at the beginning of the last 
7 days of the treatment period is in the ITT population but not the mITT population.  The mITT IS 
THE POPULATION THE ANALYSIS WILL BE DONE ON. 
 
Per Protocol Population (PP):  Any subject getting through the entire treatment period and has 
complete data (i.e., pad weight reduction data for the last 7 days of the treatment period).  For 
example, someone having only data for 6 out of the last 7 days of the treatment period is in the 
mITT population but not the PP population. 
 
Safety Population (SP):  Same as ITT. 
 
1 0 . 2   
D a t a  D e s c r i p t i o n  a n d  P r e s e n t a t i o n  
 
A statistical analysis plan (SAP) will be developed specifying in more detail the analyses for the 
study.  It will be comprised of a text section and a tables/listings/figures section.  The text will 
prescribe the outputs reported in the tables and figures; the listings will report all the data on the 
case report forms and other external data (Excel reports of laboratory data, diaries, etc.).  All 
programming will be done in SAS Version 9.4. 
 
All results will be summarized descriptively.  Continuous variable results will be tabulated using 
means, medians, standard deviations, minimums and maximums.  Categorical variables will be 
summarized using the number of observations and percentages.  p-values will be reported, 
where appropriate, to four decimal places. 
 
Intermediate calculations will not be rounded.   Internal computer precision will be kept and the 
final values will then be output, formatted to the relevant whole number and decimal precision.   
 
1 0 . 3   
S a m p l e  S i z e  a n d  S t u d y  O u t c o m e  D e t e r m i n a t i o n  
 
A precision approach will be used to determine the appropriate sample size and power for the 
study.  For power and sample size considerations a type 1 error rate (alpha) of 0.05, one-sided, 
will be used.  Given a sample size of 50 the calculations have been done with various standard 
deviations to show power below and above 90% (see Table 1 below).  Sixty to seventy 
participants will be enrolled to allow for the fifty per-protocol participants, although the analyses 
will be done on the mITT population.   
 
10          STATISTICAL  CONSIDERATIONS 

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The assumptions made for the power and sample size computations come from the Poise study 
(Ziv et al), where their assumption for the effect size was reduction in pad weight gain per 8 
hours of 70%, with a standard deviation of 15%.  The results of the study showed an 86% 
reduction in pad weight gain per 8 hours with a 9% standard deviation.  Given those results, this 
study’s assumptions of 60% improvement and a range of standard deviations from 15% to 20% 
appear conservative; thus, the expected results would indicate a successful outcome for the 
primary endpoint. 
 
The computations below are based on the precision method, which in the case of this study 
computes a lower 95% confidence limit for the percentage change.  Here we consider a changes 
around 60% in the explanation of the table.  Different standard deviations are used with the 
sample size of 50. 
 
Table 1. 
 
  n                   ½ width       Std        
                          of CI         Dev        Power 
 
  50        
 
5        16     0.999 
  50        
  
5        17     0.991 
  50        
 
5        18     0.956 
  50        
 
5        19     0.869 
  50       
  
5        20    
0.720 
  50        
 
6        20     0.995 
 
The first entry in the table shows that if the resulting mean reduction in pad weight gain was 60% 
and the standard deviation of the mean percentage change was 16%, the lower limit of the 95% 
confidence interval for 60% would be 55%: 60% - 5% (½ width), with 99.9% probability (power).  
The last line in the table above shows that the resulting mean percentage change would have to 
be greater than 56 for the power to be 99.5% (56% - 6% ½ width = 50%, not greater than 50%) if 
the standard deviation was 20%.  If the result was 60% the lower limit of the confidence interval 
would be 54%: (60% - 6%) with 99.5% power. Thus, for all lines above except 4 and 5 the 
endpoint was reached with greater than 90% power.   
 
A successful outcome for this endpoint would be any result where the lower limit of the 95% 
confidence interval is above 50% with more than 90% power, as explained above.  When the 
results are tabulated, another table will be created with the n’s and standard deviations from the 
study for comparison to the study results.   
 
Also, this sample size should also be sufficient for inferential analysis of the secondary 
endpoints. 
 
1 0 . 4   
 
S t a t i s t i c a l  H y p o t h e s e s  a n d  D a t a  D e s c r i p t i o n  
 
1. Type 1 Error and Multiplicity Concerns: 
The inferential tests for the one primary and two secondary endpoints were initially conceived to 
be one-sided using alpha=0.05.  Since the sponsor wishes to use the success of all three for 
labeling and marketing purposes, a Bonferroni adjustment for multiple comparisons will be 
employed. Thus, statistical significance will be indicated for each endpoint if the p-value is less 
than 0.0167.  
 

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2. Primary Endpoint: 
There is one primary endpoint, for efficacy.  The objective is to show that reduction in the mean 
pad weight gain per hour is >50% in the treatment period.  Thus, the null hypothesis is that the 
mean weight gain reduction per hour is <=50%, and the alternative is that it is >50%, from the 
control period (no device) to the treatment period (women wearing the device).  The data values 
will be computed for each woman as: 
 
[(total weight of all pads worn during the treatment period/hrs. pads are worn during 
treatment) 
 
minus 
 
(total weight of all pads worn during the control period/ hrs. pads are worn during 
control)] 
 
The above quantity divided by 
(total weight of all pads worn during the control period/ hrs. pads are worn during 
control) 
 
This resulting quantity is then multiplied by 100. 
 
Ex.  Subject’s total pad weight for control period is 140 grams.  Pads were worn for a total of 100 
hours. Weight/hr. is 140/100 = 1.4 g/hr.  Subject’s total pad weight for treatment period is 60 
grams.  Subject wore pads for 100 hours.  Pad weight per hour is 60/100 is 0.6 g/hr.  Difference, 
treatment – control is 0.6 -1.4 = -0.8 g/hr.  For the percent change, 100*(-0.8/1.4) =  
-57.143%.  Therefore the reduction in pad weight gain is 57.143%. 
 
The null hypothesis will be that the mean reduction in pad weight gain per hour is less than or 
equal to 50%, with the alternative that it is greater than 50%.  If the raw percentage change data 
appear to be normally distributed, a paired t-test will be used to test the hypothesis.  If not, see 
section 10.6 (2). 
 
The precision method will be utilized to determine success.  The precision approach creates a 
lower bound for a confidence interval that is higher than the reference, in this case 50%.  This 
50% standard was chosen based on the FDA guidance document.   
 
Power and sample size calculations determine scenarios of success. When the resulting mean 
reduction in pad weight gain per hour is quantified, its lower limit of a (1-0.0167)% confidence 
level is determined.  This value is then compared to parameters determined to be efficacious in 
the sample size calculations (section 10.3).  It is expected that the mean reduction per hour will 
be >50% such that the lower limit of the confidence interval for that result will be higher than 
50% with adequate power to suggest success for the study.   
 
3. Secondary Endpoints: 
 
a. For the change in SUI episodes endpoint each subject will have a change in the 
number of episodes per day from the control period to the treatment period.   
Specifically, the number of episodes will be recorded each day in the diary.  For 
the control phase, there will be (at most) 7 days of data.  The mean number of 
SUI episodes per day will be computed for each subject.  The same measures 

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will occur in the treatment period for the analysis period, the last 7 days.  Each 
subject will again have a mean number of SUI episodes per day.  If the pads are 
not worn for the entire time specified during a day, the fraction of the day the 
pads are worn will be used in computing the number of days.  Therefore, there 
will be, say, 50 differences comprised of mean number of SUI episodes per day 
in the treatment period minus mean number of SUI episodes per day for control 
period.  (These numbers will likely be negative.)  The mean of these 50 mean 
differences represents the mean change in the number of SUI episodes per day 
from the control period to the treatment period.  The null hypothesis will then be 
that the mean change in the number of SUI episodes is 0, and the alternative is 
that it is less than 0, analyzed using a paired t-test.  A p-value of less than 
0.0167 indicates success. 
 
b. For the quality of life score there will be three measures as described in the visit 
schedule above.  For descriptive purposes the results and change from the 
previous visit will be shown, as well as the change from the enrollment visit to 
the post-treatment visit.  The changes will likely be negative scores as the QOL 
is expected to improve, as the instrument records lower numbers as indicating a 
better quality of life.  For the purposes of inferential analysis, a mixed model 
analysis of variance on the scores will be used on the result at time t 
(t=baseline, post-control, post-treatment) with time as a fixed effect and subject 
as a random effect.  Thus, the null hypothesis is that there is no significant 
difference from baseline/enrollment to post-treatment, i.e., that the mean 
change in score is 0.  The alternative is that this change is less than 0.  
Correlation of scores within subjects will be considered as compound 
symmetric.  The p-value indicating the significance of the least square mean 
score at the third time-point compared to that at the first time-point will 
determine if the endpoint is met. 
 
All inferential testing will be done on the mITT population and will be one-sided.  As noted 
above statistical significance will be reached if the relevant p-value is less than 0.0167.  
Results for all populations will be reported. 
 
There is a secondary safety endpoint as described earlier in the protocol.  Safety reporting 
using urinalysis, vaginal swab, vaginal examination, and evaluation will be descriptive and 
narrative in nature.    
 
Similarly, exploratory endpoint results of comfort and successful use will be descriptive.  No 
inferential hypotheses will be used here.   
 
1 0 . 5   
A n a l y s i s  D a t a  S e t s  
 
Data will be combined into analysis data sets in a form similar to the CDISC ADaM structure, 
from which all outputs will be generated.  It is anticipated there will be the regular subject level 
data set (similar to ADSL), an efficacy data set (similar to ADEF), a laboratory data set (similar to 
ADLB), an adverse events data set (similar to ADAE), and perhaps others. 
 

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1 0 . 6   
D e s c r i p t i o n  o f  S t a t i s t i c a l  Me t h o d s  
 
1. Adjustment for non-normality: 
 
a. The primary endpoint analysis is based on the mean pad weight reduction per 
hour as a percent having a normal distribution.  Values will be checked for 
normality via the Kolmorgorov Smirnov test, and a transformation may be needed 
prior to the analysis.  First the percent change from baseline will be examined, 
and if the data are not normally distributed then a log transform of the ratio of the 
post-treatment result to the post-control will be utilized.  The standard error of this 
logged quantity and resulting lower bound of the 1- (adjusted alpha) confidence 
interval will be determined.  Then this lower bound will be exponentiated to get 
the ratio in the original data units.  100 times this value can now be interpreted as 
the percent of the post-treatment result that is left from the baseline.  This is 
because the post-treatment result will be less than the post-control result.  
Subtracting this result from 100% will give the lowest percentage value needed to 
achieve statistical significance.  If this lower bound is greater than 50% and the 
raw percent change from baseline is greater than this result then the primary 
endpoint has been reached.  
 
The expected results suggest that the percent change from baseline should be 
normal, thus validating the sample size and power calculations.  Since those 
assumptions are conservative it is felt that any transformation of the data and 
subsequent modification of the analysis (e.g., see adjustment for site below) still 
allow for this endpoint to have sufficient power. 
 
b. Secondary Endpoints:   
 
i. 
Should the difference in SUI episodes be non-normal then the natural log 
of the baseline and treatment phase scores will be taken and the natural 
log of the ratio of the post-treatment result to that of the baseline will be 
analyzed in the same fashion as described in “a” above.  A raw difference 
of 0 would translate to a ratio of 1.0 after exponentiation back. Since the 
difference is expected to be negative, the upper bound of the raw 
(transformed back) is compared to 1.  If it is less than the endpoint has 
been reached, indicating that the treatment mean is statistically 
significantly less than the control mean. 
ii. 
If the scores of the QOL indicate a significant difference from normality 
then a natural log transformation will be done and modeled  
 
2. For the other secondary analysis (safety outcomes examination) descriptive and 
possibly narrative results will be presented.  For the exploratory outcomes of comfort 
and successful usage results will be reported similarly.    Details will appear in the 
SAP. 
 

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Results for the primary and secondary endpoints will be presented in tables, with continuous 
data exhibited via descriptive summaries (n, mean (std), median, min, max); n will be a whole 
number, means, medians, and minimum and maximum values will have one decimal place, and 
standard deviation will have two.  Categorical measures (counts) reported as n (%), with n being 
a whole number and the percent having one decimal place.   
 
As mentioned above, the analyses for the primary and two secondary endpoints will be done on 
the mITT population and no imputation should be necessary.  For the primary endpoint and the 
SUI episodes secondary endpoint, by definition, the subject must have participated on one day 
of the treatment period; therefore, there will be a pad weight gain per hour measure and 
(conceivably) a diary entry for the number of SUI episodes; both of these would be the values for 
analysis for that subject.  If they are not retrievable then they are missing.  If a withdrawing mITT 
subject is able to complete the quality of life questionnaire that data would be used; if not that 
subject has a missing value for the post-treatment QOL score.  Should participants withdraw 
replacements will be utilized until 50 per protocol participants have completed the study.  
Possible screening for as many as 80 participants should provide this needed sample size.  No 
covariate use is planned for any analysis. 
 
 
 1 0 . 7  A d j u s t m e n t  f o r  S i t e  
 
The study may be performed at more than one site.  If so the effect of site will be investigated in 
each of the analyses above.   
 
For the principal endpoint analysis, a fixed effects model with site as the effect will determine if 
the percentage change from baseline or log of the ratio of post-treatment result to baseline 
result as the outcome will need to be adjusted for that effect.  A p-value of <= 0.05 will 
constitute statistical significance of the site effect. 
 
The same analysis will be done for the mean change in SUI episodes per day secondary 
endpoint analysis.  Site will be a fixed effect modeling each subject’s change in mean number of 
SUI episodes per day. 
 
For the quality of life repeated measures ANOVA site will again be included in the model as a 
fixed effect. 
 
Should site become statistically significant in any of the analyses then it will be used as a fixed 
effect factor in all three analyses, and the appropriate percentage and mean changes (or log 
transformations implementing those analyses) will be extracted from the output created by the 
models. 
 
  1 0 . 8  A d v e r s e  E v e n t s  
 
No formal testing of adverse events or their characteristics will be performed.  Reporting is 
described above.  The latest version of MedDRA will be used for coding.  The section of tables 
will include a summary table, a system organ class/preferred term table, and tables for 
relationship and severity to study treatments.  
 
1 0 . 9  I n t e r i m  A n a l y s e s  a n d  S t o p p i n g  C r it e r i a .  
 
No interim analyses are planned, and the study will be run to its completion unless stopped for 
safety considerations. 

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Each participating site will maintain appropriate medical and research records for this trial, in 
compliance with ICH E6 and regulatory and institutional requirements for the protection of 
confidentiality of participants. As part of participating in a NIH IC-sponsored or NIH IC -affiliated 
study, each site will permit authorized representatives of the NIH IC and regulatory agencies 
to examine (and when permitted by applicable law, to copy) clinical records for the purposes 
of quality assurance reviews, audits, and evaluation of the study safety, progress, and data 
validity. Describe in this section who will have access to records. 
 
 
.  
Following written SOPs, the monitors will verify that the clinical trial is conducted and data are 
generated, documented (recorded), and reported in compliance with the protocol, GCP, and the 
applicable regulatory requirements (e.g., Good Laboratory Practices (GLP), Good 
Manufacturing Practices (GMP)). 
The investigational site will provide direct access to all trial related sites, source data/documents, 
and reports for the purpose of monitoring and auditing by the sponsor, and inspection by local 
and regulatory authorities. 
 
 
  1 3 .1      E T H I C A L   S T A N D A R D                                                                                                                                        
The investigator will ensure that this study is conducted in full conformity with Regulations 
for the Protection of Human Participants of Research codified in 45 CFR Part 46, 21 CFR 
Part 50, 21 CFR Part 56, and/or the ICH E6. 
  1 3 .2 I N S T I T U T I O N A L R E V I E W B O A R D                                                                                                                
The protocol, informed consent form(s), recruitment materials, and all participant materials 
will be submitted to the IRB for review and approval. Approval of both the protocol and the 
consent form must be obtained before any participant is enrolled. Any amendment to the 
protocol will require review and approval by the IRB before the changes are implemented to 
the study. All changes to the consent form will be IRB approved; a determination will be made 
regarding whether previously consented participants need to be re-consented. 
 
  1 3 .3 I N F O R M E D C O N S E N T P R O C E S S                                                                                                                  
13.3.1 CONSENT/ASSENT AND OTHER INFORMATIONAL DOCUMENTS PROVIDED 
TO PARTICIPANTS Consent forms describing in detail the study agent, study procedures, 
and risks are given to the participant, and written documentation of informed consent is 
required prior to starting intervention/administering study product. The following consent 
materials are submitted with this protocol Rinovum Subsidiary 2, LLC. SUI Device Efficacy 
and Safety Study Informed Consent. 
 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate 
in the study and continues throughout the individual’s study participation. Extensive 
discussion of risks and possible benefits of participation will be provided to the participants 
and their families. Consent forms will be IRB-approved and the participant will be asked to 
read and review the document. The investigator will explain the research study to the 
participant and answer any questions that may arise. All participants will receive a verbal 
explanation in terms suited to their comprehension of the purposes, procedures, and 
potential risks of the study and of their rights as research participants. Participants will have 
11          SOURCE  DOCUMENTS  AND  ACCESS  TO  SOURCE  DATA/DOCUMENTS 
12          QUALITY  ASSURANCE  AND  QUALITY  CONTROL 
13          ETHICS/PROTECTION  OF  HUMAN  SUBJECTS 

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the opportunity to carefully review the written consent form and ask questions prior to 
signing. 
 
The participants will have the opportunity to discuss the study with their surrogates or think 
about it prior to agreeing to participate. The participant will sign the informed consent 
document prior to any procedures being done specifically for the study. The participants may 
withdraw consent at any time throughout the course of the trial. A copy of the informed 
consent document will be given to the participants for their records. The rights and welfare of 
the participants will be protected by emphasizing to them that the quality of their medical care 
will not be adversely affected if they decline to participate in this study. 
 
  1 3 . 4 P A R T I C I P A N T AND D A T A C O N F I D E N T I A L I T Y                                                                            
Participant 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 in addition to the clinical information relating to 
participants. Therefore, 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, other authorized representatives of the sponsor, representatives of the IRB 
or pharmaceutical company supplying study product 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 participants in this study. The clinical 
study site will permit access to such records. 
 
The study participant’s contact information will be securely stored at each clinical site for 
internal use during the study. At the end of the study, all records will continue to be kept in a 
secure location for as long a period as dictated by local IRB and Institutional regulations. 
 
Study participant research data, which is for purposes of statistical analysis and scientific 
reporting, will be transmitted to and stored at the East Suburban OB/GYN Facility. This will 
not include the participant’s contact or identifying information. Rather, individual participants 
and their research data will be identified by a unique study identification number. The study 
data entry and study management systems used by clinical sites and by the [insert institution] 
research staff will be secured and password protected. At the end of the study, all study 
databases will be de-identified and archived at the [insert institution]. 
 
  1 3 . 5 F U T U R E U S E O F S T O R E D S P E C I M E N S                                                                                       
Data collected for this study will be analyzed and stored at the [insert institution] facility.  After 
the study is completed, the de-identified, archived data will be transmitted to and stored at the 
Sponsor’s facility under the supervision of the Director of Regulatory and Quality for use by 
other researchers including those outside of the study. Permission to transmit data to the will 
be included in the informed consent. 
 
  1 4 . 1 D A T A C O L L E C T I O N A N D M A N A G E M E N T R E S P O N S I B I L I T I E S                                            
Data collection is the responsibility of the clinical trial staff at the site under the supervision of 
the site PI. The investigator is responsible for ensuring the accuracy, completeness, legibility, 
and timeliness of the data reported. 
 
14          DATA  HANDLING  AND  RECORD  KEEPING 

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All source documents should be completed in a neat, legible manner to ensure accurate 
interpretation of data. Black 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 participant 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 and captured in a progress note and maintained in the participant’s 
official electronic study record. 
 
Clinical data (including AEs, concomitant medications, and expected adverse reactions data) 
and clinical laboratory data will be entered into Case Report Forms manually.  
 
  1 4 . 2 S T U D Y R E C O R D S R E T E N T I O N                                                                                                        
Study documents should 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 should 
be retained for a longer period, however, if required by local regulations. No records will be 
destroyed without the written consent of the sponsor, if applicable. It is the responsibility of the 
sponsor to inform the investigator when these documents no longer need to be retained. 
 
  1 4 . 3 P R O T O C O L D E V I A T I O N S                                                                                                                   
A protocol deviation is any noncompliance with the clinical trial protocol, GCP, or MOP 
requirements. The noncompliance may be either on the part of the participant, the 
investigator, 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 3 working days of the scheduled protocol-required activity. All deviations must be 
addressed in study source documents, reported the Sponsor. Protocol deviations must be 
sent to the local IRB per their guidelines. The site PI/study staff is responsible for knowing 
and adhering to their IRB requirements. Further details about the handling of protocol 
deviations will be included in the MOP.] 
  1 4 . 4 P U B L I C A T I O N A N D D A T A S H A R I N G P O L I C Y                                                                              
This study will comply with the NIH Public Access Policy, which ensures that the public has 
access to the published results of NIH funded research. It requires scientists to submit final 
peer-reviewed journal manuscripts that arise from NIH funds to the digital archive PubMed 
Central upon acceptance for publication. 
 
The International Committee of Medical Journal Editors (ICMJE) member journals have 
adopted a clinical trials registration policy as a condition for publication. The ICMJE defines a 
clinical trial as any research project that prospectively assigns human participants to 
intervention or concurrent comparison or control groups to study the cause-and-effect 

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relationship between a medical intervention and a health outcome. Medical interventions 
include drugs, surgical procedures, devices, behavioral treatments, process-of-care changes, 
and the like. Health outcomes include any biomedical or health-related measures obtained in 
patients or participants, including pharmacokinetic measures and adverse events. The ICMJE 
policy, and the Section 801 of the Food and Drug Administration Amendments Act of 2007, 
requires that all clinical trials be registered in a public trials registry such as ClinicalTrials.gov, 
which is sponsored by the National Library of Medicine. Other biomedical journals are 
considering adopting similar policies. For interventional clinical trials performed under NIH IC 
grants and cooperative agreements, it is the grantee’s responsibility to register the trial in an 
acceptable registry, so the research results may be considered for publication in ICMJE 
member journals. The ICMJE does not review specific studies to determine whether 
registration is necessary; instead, the committee recommends that researchers who have 
questions about the need to register err on the side of registration or consult the editorial 
office of the journal in which they wish to publish. 
 
FDAAA mandates that a "responsible party" (i.e., the sponsor or designated principal 
investigator) register and report results of certain "applicable clinical trials": 
 
• 
Trials of Drugs and Biologics: Controlled, clinical investigations, other than Phase I 
investigations, of a product subject to FDA regulation; 
• 
Trials of Devices: Controlled trials with health outcomes of a product subject to FDA 
regulation (other than small feasibility studies) and pediatric post-market 
surveillance studies. 
 
NIH grantees must take specific steps to ensure compliance with NIH implementation of 
FDAAA.] 
 
 
The independence of this study from any actual or perceived influence, such as by the 
pharmaceutical industry, is critical. Therefore, any actual conflict of interest of persons who 
have a role in the design, conduct, analysis, publication, or any aspect of this trial will be 
disclosed and managed. Furthermore, persons who have a perceived conflict of interest will 
be required to have such conflicts managed in a way that is appropriate to their participation 
in the trial.  
 
Bargen, et al. Cost Utility of the Treatment of Stress Urinary Incontinence, 2015 
Farrell, et al. Effectiveness of a new self-positioning pessary for the management of urinary 
incontinence in women, 2007. 
Komesu, et al. Restoration of continence by pessaries: magnetic resonance imaging 
assessment of mechanism of action, 2008. 
Mark Deutchman, Meghan Wulster-Radcliffe. Stress Urinary Incontinence in Women: Diagnosis 
and Medical Management, 2005. 
Nystrom, et al. ICIQ Symptom and Wuality of Life Instruments Measure Clinically Relevant 
Improvements in Women with Stress Urinary Incontinence, 2013. 
15          CONFLICT  OF  INTEREST  POLICY 
16          LITERATURE  REFERENCES 

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Rogers, Rebecca G. Urinary Stress Incontinence in Women, 2008. 
Rovner, Eric S, and Alan J Wein. “Treatment Options for Stress Urinary Incontinence.” Reviews 
in Urology 6.Suppl 3 (2004): S29–S47. Print. 
Schaffer, et al. Predictors of Success and Satisfaction of Nonsurgical Therapy for Stress Urinary 
Incontinence, 2012. 
Shamliyan, et al. Systematic Review: Randomized, Controlled Trials of Nonsurgical Treatments 
for Urinary Incontinence in Women, 2008. 
Shamliyan, Tatyana A. "Systematic Review: Randomized, Controlled Trials of Nonsurgical 
Treatments for Urinary Incontinence in Women." Annals of Internal Medicine 148.6 (2008): 
459. Annuals.org. Web. 25 Apr. 2017. 
Thyssen, H., J. Bidmead, G. Lose, K. MÃ¸ller Bek, P. Dwyer, and L. Cardozo. "A New 
Intravaginal Device for Stress Incontinence in Women." BJU International 88.9 (2002): 889-
92. Wiley Online Library. Web. 25 Apr. 2017 
Ziv E, Stanton SL, Abarbenel J. Efficacy and safety of a novel disposable intravaginal device for 
treating stress urinary incontinence. Am J Obstet Gynocol 2008; 198:594.e1 – 594.e7