A Study to Assess Efficacy and Safety With Solifenacin Succinate to Improve Urinary Continence After Robotic Assisted Radical Prostatectomy

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy and safety of 12 weeks of treatment of solifenacin succinate versus placebo in participants who are incontinent after Robotic Assisted Radical Prostatectomy. This study will also assess the effect of 12 weeks of treatment with solifenacin succinate versus placebo on quality of life (QOL) as measured by questionnaires.

Detailed Description
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The study duration includes a 14-day treatment free wash-out period. The maximum total study duration is 15 weeks (2-3 week screening/washout period and a 12 week treatment period). The Baseline, Week 4, and Week 8 visits will be telephone contact visits. Participants will complete an electronic daily pad use diary during the study duration. Participants will also be asked to complete several questionnaires during the study.

Official Title
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A Randomized, Double-Blind, Parallel, Placebo-Controlled, Phase 4, Multicenter Study to Assess Efficacy and Safety of VESIcare® (Solifenacin Succinate) to Improve Urinary Continence of Subjects After Robotic Assisted Radical Prostatectomy

Conditions
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Urinary Incontinence

Intervention / Treatment
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* Drug: solifenacin succinate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ambulatory Willing and able to complete the daily pad use diary, American Urology Association Symptom Score (AUASS) with Bother Score, the International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF), and the Work Productivity and Activity Impairment Questionnaire (WPAI) Has not used any medication for over-active bladder symptoms for at least 14 days prior to enrollment Diagnosed with prostate cancer, treated by Robotic Assisted Radical Prostatectomy, is voiding spontaneously and has urinary incontinence one week after removal of the indwelling catheter which requires management with 2 to 10 pads inclusive per day (24 hour days) for 7 consecutive days Exclusion Criteria: Evidence of severe neurologic damage post-prostatectomy Evidence of chronic urologic inflammation such as interstitial cystitis and bladder stone; uncontrolled narrow angle glaucoma; urinary or gastric retention or neurogenic bladder Symptomatic for urinary tract infection or has a urine culture result which requires treatment as determined by the investigator. Clinically significant history of hepatic or renal impairment (2 X Upper Limit of Normal (ULN) values in alanine aminotransferase (ALT), aspartate aminotransferase (AST) or creatinine clearance < 30 ml/min) History of diagnosed gastrointestinal obstruction disease Any prior history of local radiation therapy to the prostate or rectum or any prior hormonal therapy or has planned such therapy during study conduct Known or suspected hypersensitivity to solifenacin succinate, any components, or other anticholinergics Treated with any investigational drug within last 30 days History of a clinically significant illness or medical condition that would preclude participation in the study Diagnosed with New York Heart Association Class III and IV heart failure Any of the following peri-operative laboratory results: ALT > 2.0 ULN, AST > 2.0 ULN, serum creatinine > 1.5 mg/L, blood glucose > 130 mg/dL, blood urea nitrogen (BUN) > 23 mg/dL. Severe hypertension on peri-operative evaluation which is defined as a sitting systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 110 mmHg, and which is not corrected Electrolytes (sodium, potassium, chloride or bicarbonate) that are not in normal range and clinically significant as determined by the investigator in the perioperative period. Can be eligible if electrolytes are corrected to within normal range prior to randomization Participated in any interventional clinical study or has been treated with any investigational drugs within 30 days or 5 half lives, whichever is longer, prior to the initiation of Screening.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Solifenacin succinate<br>Participants received 5 mg solifenacin succinate tablets once a day for 12 weeks. At week 4, based on efficacy and safety and in agreement with the investigator, the dose might be increased to 10 mg (2 tablets of 5 mg) once daily. | Drug: solifenacin succinate<br>* oral<br>* Other names: YM905;|
| Placebo Comparator: Placebo<br>Participants received matching placebo tablets once a day for 12 weeks. | Drug: Placebo<br>* oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time From First Dose to Urinary Continence | Urinary continence is defined as the first of three consecutive 24-hour days in which a participant uses no pads, or a pad for security which remains completely dry, during the 12-week treatment period. Participants recorded their daily pad usage in an electronic diary. Kaplan-Meier curves were used to estimate the distribution of cumulative incidence of urinary continence over the 12-week study treatment period. Participants who did not experience the event during the 12-week treatment period were considered as censored at the End of Treatment (EOT) visit or Week 12, whichever occurs first. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Gain Continence During 12-week Treatment Period | Urinary continence is defined as three consecutive 24-hour days in which a participant uses no pads or a pad for security which remains completely dry. Participants recorded their daily pad usage in an electronic diary during the 12-week treatment period. End of treatment is the last on-treatment assessment during the treatment period. | Weeks 4, 8, and 12 | 
| Average Daily Pad Usage at Baseline | Participants recorded their daily pad usage in an electronic diary during the 12-week treatment period. A 7-day window was used to calculate the average daily pad usage. | Baseline (7 days prior to Day 1) | 
| Change From Baseline in Average Daily Pad Usage | Participants recorded their daily pad usage in an electronic diary during the 12-week treatment period. A 7-day window was used to calculate the average daily pad usage. End of treatment is the last on-treatment assessment during the treatment period. | Baseline and Weeks 4, 8 and 12 | 
| American Urology Association Symptom Score (AUASS) at Baseline | Quality of life was measured by the American Urology Association Symptom Score (AUASS). The AUASS includes 7 questions addressing symptoms of frequency, urgency, nocturia (waking during the night to urinate), hesitancy, weak urinary, incomplete emptying, and intermittence. The questionnaire asked participants to consider how these symptoms affected them over the past month on a scale from 0 (not at all) to 5 (almost always). The AUASS is a sum of the 7 symptom scores and ranges from 0 (best) to 35 (worst). | Baseline | 
| Change From Baseline in American Urology Association Symptom Score (AUASS) | Quality of life was measured by the American Urology Association Symptom Score (AUASS). The AUASS includes 7 questions addressing symptoms of frequency, urgency, nocturia (waking during the night to urinate), hesitancy, weak urinary, incomplete emptying, and intermittence. The questionnaire asked participants to consider how these symptoms affected them over the past month on a scale from 0 (not at all) to 5 (almost always). The AUASS Symptom Score is a sum of the 7 symptom scores and ranges from 0 (best) to 35 (worst). End of treatment is the last on-treatment assessment during the treatment period. | Baseline and Week 12 | 
| American Urology Association Quality of Life (QOL) Score at Baseline | The American Urology Association (AUA) includes a single bother question which asked participants how they would feel if they had to live with their urinary condition the way it is now for the rest of their life. The bother question score ranges from 0 (delighted) to 6 (terrible). | Baseline | 
| Change From Baseline in American Urology Association Quality of Life (QOL) Score | The American Urology Association (AUA) includes a single bother question which asked participants how they would feel if they had to live with their urinary condition the way it is now for the rest of their life. The bother question score ranges from 0 (delighted) to 6 (terrible). End of treatment is the last on-treatment assessment during the treatment period. | Baseline and Week 12 | 
| International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) QOL Score at Baseline | The ICIQ-SF is a validated self-administered questionnaire designed for patients with urinary incontinence. The ICIQ-SF assessed urinary incontinence using 3 scored questions which ask patients about their frequency of urine leakage, how much urine leakage, and perceived impact of leakage on daily lives over the past 4 weeks. The ICIQ-SF is a sum of the 3 scores and ranges from 0 (low bother) to 21 (maximum bother). | Baseline | 
| Change From Baseline in International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) QOL Score | The ICIQ-SF is a validated self-administered questionnaire designed for patients with urinary incontinence. The ICIQ-SF assessed urinary incontinence using 3 scored questions which ask patients about their frequency of urine leakage, how much urine leakage, and perceived impact of leakage on daily lives over the past 4 weeks. The ICIQ-SF is a sum of the 3 scores and ranges from 0 (low bother) to 21 (maximum bother). | Baseline and Week 12 | 
| Baseline Work Productivity and Activity Impairment (WPAI): Percent Work Time Missed | Work productivity was measured by the Work Productivity and Activity Impairment Questionnaire (WPAI). WPAI asks participants about the effect of urinary leakage on their ability to perform their work-related functions and carry out daily activities over the past seven days. Percent work time missed is derived from the number of hours of work missed due to urinary leakage as a percentage of total hours that should have been worked. A higher percentage indicates more hours missed. | Baseline | 
| Change From Baseline in Work Productivity and Activity Impairment (WPAI): Percent Work Time Missed | Work productivity was measured by the Work Productivity and Activity Impairment Questionnaire (WPAI). WPAI asks participants about the effect of urinary leakage on their ability to perform their work-related functions and carry out daily activities over the past seven days. Percent work time missed is derived from the number of hours of work missed due to urinary leakage as a percentage of total hours that should have been worked. A higher percentage indicates more hours missed. A negative change from Baseline indicates improvement. | Baseline and Week 12 | 
| Baseline Work Productivity and Activity Impairment (WPAI): Percent Impairment While Working | Work productivity was measured by the Work Productivity and Activity Impairment Questionnaire (WPAI). WPAI asks participants about the effect of urinary leakage on their ability to perform their work-related functions and carry out daily activities over the past seven days. Percent impairment while working was derived from the participant's assessment of the degree to which urinary leakage affected their productivity while working. A higher percentage indicates greater impairment and less productivity. | Baseline | 
| Change From Baseline in Work Productivity Assessment Index (WPAI): Percent Impairment While Working | Work productivity was measured by the Work Productivity and Activity Impairment Questionnaire (WPAI). WPAI asks participants about the effect of urinary leakage on their ability to perform their work-related functions and carry out daily activities over the past seven days. Percent impairment while working was derived from the participant's assessment of the degree to which urinary leakage affected their productivity while working. A higher percentage indicates greater impairment and less productivity. A negative change from Baseline indicates improvement. | Baseline and Week 12 | 
| Baseline Work Productivity and Activity Impairment (WPAI): Percent Overall Work Impairment | Work productivity was measured by the Work Productivity and Activity Impairment Questionnaire (WPAI). WPAI asks participants about the effect of urinary leakage on their ability to perform their work-related functions and carry out daily activities over the past seven days. Percent overall work impairment takes into account both hours missed due to urinary leakage and the participant's assessment of the degree to which urinary leakage affected their productivity while working. A higher percentage indicates greater impairment and less productivity. | Baseline | 
| Change From Baseline in Work Productivity and Activity Impairment (WPAI): Percent Overall Work Impairment | Work productivity was measured by the Work Productivity and Activity Impairment Questionnaire (WPAI). WPAI asks participants about the effect of urinary leakage on their ability to perform their work-related functions and carry out daily activities over the past seven days. Percent overall work impairment takes into account both hours missed due to urinary leakage and the participant's assessment of the degree to which urinary leakage affected their productivity while working. A higher percentage indicates greater impairment and less productivity. A negative change from Baseline indicates improvement. | Baseline and Week 12 | 
| Baseline Work Productivity and Activity Impairment (WPAI): Percent Activity Impairment | Work productivity was measured by the Work Productivity and Activity Impairment Questionnaire (WPAI). WPAI asks participants about the effect of urinary leakage on their ability to perform their work-related functions and carry out daily activities over the past seven days. Percent activity impairment is derived from the participant's assessment of the degree to which their urinary leakage affected their regular daily activities. A higher percentage indicates greater impairment and less productivity. | Baseline | 
| Change From Baseline in Work Productivity and Activity Impairment (WPAI): Percent Activity Impairment | Work productivity was measured by the Work Productivity and Activity Impairment Questionnaire (WPAI). WPAI asks participants about the effect of urinary leakage on their ability to perform their work-related functions and carry out daily activities over the past seven days. Percent activity impairment is derived from the participant's assessment of the degree to which their urinary leakage affected their regular daily activities. A higher percentage indicates greater impairment and less productivity. A negative change from Baseline indicates improvement. | Baseline and Week 12 | 
| Time From Baseline to First Day of Returning to Work | The time from Baseline to first day of returning to work was estimated using the Kaplan-Meier method. | From Baseline to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Radical Robotic Arm, Vesicare, Post Prostatectomy Incontinence, YM905