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

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

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.

Study Overview

• Status: Completed
• Conditions: Urinary Incontinence
• Intervention / Treatment: Drug: Placebo; Drug: solifenacin succinate

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 640
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z IM9
      • The Prostate Centre, Diamond Health Care Centre
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network/ Princess Margaret Hospital
• United States
  • Alabama
    • Homewood, Alabama, United States, 35209
      • Urology Centers of Alabama
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Alaska Clinical Research Center
  • Arizona
    • Tucson, Arizona, United States, 85715
      • Urological Associates of Southern Arizona
  • California
    • La Jolla, California, United States, 92093
      • University of California, San Diego Moores Cancer Center
    • Los Angeles, California, United States, 90048
      • Tower Urology
    • Sacramento, California, United States, 95815
      • Radiological Associates of Sacramento Medical Group, Inc.
  • Colorado
    • Denver, Colorado, United States, 80211
      • Urology Center of Colorado
    • Englewood, Colorado, United States, 80113
      • Urology Associates
    • Parker, Colorado, United States, 80134
      • Advanced Urology
  • Connecticut
    • Middlebury, Connecticut, United States, 06762
      • Connecticut Clinical Research Center
    • New Britain, Connecticut, United States, 06052
      • Grove Hill Medical Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20036
      • Urologic Surgeons of Washington
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Hialeah, Florida, United States, 33016
      • Urology Research Network
    • Jacksonville, Florida, United States, 32204
      • East Coast Institute for Research
    • Orlando, Florida, United States, 32803
      • Winter Park Urology Associates
    • Tallahassee, Florida, United States, 32308
      • Southeastern Research Group
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Springfield, Illinois, United States, 62703
      • Springfield Clinic
  • Indiana
    • Fort Wayne, Indiana, United States, 46825
      • Northeast Indiana Research
    • Greenwood, Indiana, United States, 46143
      • Urology of Indiana
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • The University of Iowa Hospitals and Clinics
    • West Des Moines, Iowa, United States, 50266
      • The Iowa Clinic
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University School of Medicine, Department of Urology
  • Massachusetts
    • Burlington, Massachusetts, United States, 01805
      • Lahey Clinic Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Grand Rapids, Michigan, United States, 49546
      • Spectrum Health Medical Group
  • Minnesota
    • Sartell, Minnesota, United States, 56377
      • Adult and Pediatric Urology Group
  • Montana
    • Missoula, Montana, United States, 59808
      • Five Valley Urology
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • South Nevada Aids Research
  • New Jersey
    • Lawrenceville, New Jersey, United States, 08648
      • AdvanceMed Research
    • Mount Laurel, New Jersey, United States, 08043
      • Delaware Valley Urology
    • New Brunswick, New Jersey, United States, 08901
      • Robert Wood Johnson Medical School
  • New York
    • Albany, New York, United States, 12208
      • Community Care Physicians PC
    • Brooklyn, New York, United States, 11215
      • Brooklyn Urology Research Group
    • New York, New York, United States, 10016
      • University Urology Associates
    • Poughkeepsie, New York, United States, 12601
      • Hudson Valley Urology, PC
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
    • Syracuse, New York, United States, 13210
      • AMP Urology
  • North Carolina
    • Cary, North Carolina, United States, 27511
      • Cary Urology
    • Raleigh, North Carolina, United States, 27607
      • Associated Urologists of North Carolina
  • Ohio
    • Cincinnati, Ohio, United States, 45212
      • The Urology Group
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Toledo, Ohio, United States, 43615
      • Romius Institute of Northwest Ohio
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Bala-Cynwyd, Pennsylvania, United States, 19004
      • Urologic Consultants of Southeastern Pennsylvania
  • Rhode Island
    • East Providence, Rhode Island, United States, 02915
      • Pharma Resources
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • Academic Urologists
    • Knoxville, Tennessee, United States, 37920
      • Volunteer Research Group
    • Memphis, Tennessee, United States, 38119
      • Southeast Urology Network
  • Texas
    • Dallas, Texas, United States, 75231
      • Urology Clinics of North Texas
    • Houston, Texas, United States, 77030
      • Methodist Hospital Research Institute
    • Houston, Texas, United States, 77094
      • Methodist Urology Associates
    • San Antonio, Texas, United States, 78229
      • Urology San Antonio Research
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center
    • Seattle, Washington, United States, 98104
      • Swedish Urology Group
  • West Virginia
    • Charleston, West Virginia, United States, 25304
      • CAMC Institute Clinical Trial Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Solifenacin succinate; 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; oral; Other Names: Vesicare; YM905
PLACEBO_COMPARATOR: Placebo; Participants received matching placebo tablets once a day for 12 weeks.	Drug: Placebo; oral

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc

Publications and helpful links

Helpful Links

• Link to results on the Astellas Clinical Study Results website.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 2, 2011
• Primary Completion (ACTUAL): October 21, 2013
• Study Completion (ACTUAL): October 21, 2013

Study Registration Dates

• First Submitted: June 10, 2011
• First Submitted That Met QC Criteria: June 10, 2011
• First Posted (ESTIMATE): June 13, 2011

Study Record Updates

• Last Update Posted (ACTUAL): August 28, 2018
• Last Update Submitted That Met QC Criteria: July 31, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Vesicare; YM905; Radical Robotic Arm; Post Prostatectomy Incontinence
• Additional Relevant MeSH Terms: Urologic Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Urination Disorders; Urinary Incontinence; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Urological Agents; Solifenacin Succinate
• Other Study ID Numbers: 905-UC-050

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Access to anonymized individual participant level data collected during the trial, in addition to study-related supporting documentation, is planned for trials conducted with approved product indications and formulations, as well as compounds terminated during development. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.
• IPD Sharing Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• IPD Sharing Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR