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Dysport® Treatment of Urinary Incontinence in Adults Subjects With Neurogenic Detrusor Overactivity (NDO) Due to Spinal Cord Injury or Multiple Sclerosis - Study 1

Phase 3
Terminated
Conditions
Urinary Incontinence
Overactive Bladder
Interventions
Biological: Botulinum toxin type A
Drug: Placebo
Registration Number
NCT02660138
Lead Sponsor
Ipsen
Brief Summary

The purpose of this study is to provide confirmatory evidence of the safety and efficacy of two Dysport® (AbobotulinumtoxinA) doses (600 units \[U\] and 800 U), compared to placebo in reducing urinary incontinence (UI) in adult subjects treated for neurogenic detrusor overactivity (NDO) due to spinal cord injury (SCI) or multiple sclerosis (MS).

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
227
Inclusion Criteria
  • Urinary Incontinence for at least 3 months prior to Screening as a result of Neurogenic Detrusor Overactivity due to Spinal Cord Injury or Multiple Sclerosis.
  • Subjects with Spinal Cord Injury must have a stable neurological injury at T1 level or below which occurred at least 6 months prior to Screening.
  • Subjects with Multiple Sclerosis must be clinically stable in the investigator's opinion, with no exacerbation (relapse) of MS for at least 3 months prior to Screening.
  • Subjects must have had an inadequate response after at least 4 weeks of oral medications used in the treatment of NDO (e.g. anticholinergics, beta-3 agonists) and/or have intolerable side-effects.
  • Routinely performing Clean Intermittent Catheterization (CIC) to ensure adequate bladder emptying.
  • An average of at least two episodes per day of Urinary Incontinence recorded on the screening bladder diary.

Key

Exclusion Criteria
  • Any current condition (other than NDO) that may impact on bladder function.
  • Previous or current, tumour or malignancy affecting the spinal column or spinal cord, or any other unstable cause of SCI.
  • Any condition that will prevent cystoscopic treatment administration or CIC usage, e.g. urethral strictures.
  • Current indwelling bladder catheter, or removal of indwelling bladder catheter less than 4 weeks prior to Screening.
  • BTX-A treatment within 9 months prior to Screening for any urological condition (e.g. detrusor or urethral sphincter treatments).
  • Any neuromodulation/electrostimulation usage for urinary symptoms/incontinence within 4 weeks prior to Screening. Any implanted neuromodulation device must be switched off at least 4 weeks prior to Screening.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
800 U Dysport® GroupBotulinum toxin type A-
600 U Dysport® GroupBotulinum toxin type A-
600 U Dysport® Placebo GroupPlacebo-
800 U Dysport® Placebo GroupPlacebo-
Primary Outcome Measures
NameTimeMethod
Mean Change From Baseline in Weekly Number of UI Episodes at Week 6 of DBPC CycleBaseline and Week 6 of DBPC Cycle

The weekly number of UI episodes was measured using a 7-day bladder diary. Bladder diaries that contained data recorded on at least 5 days were included in the analysis. The least square (LS) mean of the change in weekly number of UI episodes at 6 weeks after the first study treatment was calculated using a mixed model repeated measures (MMRM) analysis.

Secondary Outcome Measures
NameTimeMethod
Mean Change From Baseline in Maximum Cystometric Capacity (MCC) at Week 6 of DBPC CycleBaseline and Week 6 of DBPC Cycle

All subjects had a standardised urodynamic (filling cystometry) assessment at baseline (screening) and again at Week 6 to determine the MCC. The LS mean of the change in MCC at 6 weeks after the first study treatment was calculated using an analysis of covariance (ANCOVA).

Mean Change From Baseline in Maximum Detrusor Pressure (MDP) at Week 6 of DBPC CycleBaseline and Week 6 of DBPC Cycle

All subjects had a standardised urodynamic filling cystometry assessment at baseline (screening) and again at Week 6 to determine the MDP. The LS mean of the change in MDP at 6 weeks after the first study treatment was calculated using an ANCOVA.

Number of Subjects With No Episodes of UI at Week 6 of DBPC CycleBaseline and Week 6 of DBPC Cycle

The weekly number of UI episodes was measured using a 7-day bladder diary. Bladder diaries that contained data recorded on at least 5 days were included in the analysis. The number of subjects with no UI episodes at 6 weeks after the first study treatment was recorded and the percentage of subjects was also calculated from the total number of subjects with any number of UI events at Week 6.

Number of Subjects With No IDCs During Storage at Week 6 of DBPC CycleBaseline and Week 6 of DBPC Cycle

All subjects had a standardised urodynamic filling cystometry assessment at baseline (screening) and again at Week 6 to determine the occurrence of IDCs. The number of subjects without IDCs at 6 weeks after the first study treatment was recorded and the percentage of subjects was also calculated from the total number of subjects with data available for analysis at Week 6.

Mean Change From Baseline in Incontinence Quality of Life (I-QoL) Questionnaire Total Summary Score at Week 6 of DBPC CycleBaseline and Week 6 of DBPC Cycle

The I-QoL questionnaire is a validated, disease-specific questionnaire designed to measure the effect of UI on subjects' QoL. It consists of 22 items in 3 domains (avoidance and limiting behaviour, psychosocial impact and social embarrassment). Subjects used a 5-point response scale for each of the 22 items with values ranging from 1 (extremely) to 5 (not at all). The total summary score was transformed to a 100 point scale ranging from 0 to 100, with higher scores indicating a better QoL. The LS mean of the change in the I-QoL total summary score at 6 weeks after the first study treatment was calculated using a MMRM analysis.

Number of Subjects With a UI Response at Improvement Levels ≥30%, ≥50%, and ≥75% at Week 6 of the DBPC CycleBaseline and Week 6 of DBPC Cycle

The weekly number of UI episodes was measured using a 7-day bladder diary. Bladder diaries that contained data recorded on at least 5 days were included in the analysis. The number of baseline UI episodes was compared with the number of UI episodes at Week 6 to determine the level of response each subject reached, i.e. a decrease of ≥30%, ≥50% or ≥75% . The number of subjects showing an improvement of ≥30%, ≥50% and ≥75% were recorded and the percentage of subjects was also calculated from the total number of subjects with any number of UI events at Week 6.

Mean Change From Baseline in Volume at First Involuntary Detrusor Contraction (Vol@1stIDC) at Week 6 of DBPC CycleBaseline and Week 6 of DBPC Cycle

All subjects had a standardised urodynamic (filling cystometry) assessment at baseline (screening) and again at Week 6 to determine the Vol@1stIDC which is the instilled volume when first IDC commences. Subjects who did not exhibit a post-treatment IDC at Week 6 had Vol@1stIDC imputed using the recorded corrected MCC volume at Week 6. The LS mean of the change in Vol@1stIDC at 6 weeks after the first study treatment was calculated using an ANCOVA.

Mean Change From Baseline in Volume Per Void at Week 6 of DBPC CycleBaseline and Week 6 of DBPC Cycle

The volume per void was measured during one 24-hour period of the 7-day bladder diary. The LS mean of the change in volume per void at 6 weeks after the first study treatment was calculated using a MMRM analysis.

Median Time Between TreatmentsDay of first treatment (baseline) and day of retreatment, up to 2 years

Duration of effect for time between treatments was calculated by: (the date of the first retreatment visit - date of first treatment administration in the DBPC cycle). The median number of days between treatments was determined based on the Kaplan-Meier method. Subjects with no retreatment were censored at the last visit.

Trial Locations

Locations (80)

USC Norris Comprehensive Cancer Center

🇺🇸

Los Angeles, California, United States

Urology Clinics of North Texas

🇺🇸

Dallas, Texas, United States

Delaware Valley Urology,IIC

🇺🇸

Voorhees, New Jersey, United States

Louis Stokes Cleveland Veterans Affairs Medical Center

🇺🇸

Cleveland, Ohio, United States

Cleveland Clinic

🇺🇸

Cleveland, Ohio, United States

Radboud UMC

🇳🇱

Nijmegen, Netherlands

Szpital Kliniczny Dzieciątka Jezus w Warszawie

🇵🇱

Warszawa, Poland

VU University Medical Center

🇳🇱

Amsterdam, Netherlands

Hospital de Braga

🇵🇹

Braga, Portugal

British Hospital

🇵🇹

Lisboa, Portugal

Erasmus MC

🇳🇱

Rotterdam, Netherlands

Wojewódzki Szpital Zespolony w Elblągu

🇵🇱

Elblag, Poland

NZOZ Heureka

🇵🇱

Piaseczno, Poland

EuroMediCare Szpital Specjalistyczny z Przychodnią we Wrocławiu

🇵🇱

Wroclaw, Poland

Spitalul Clinic Colentina

🇷🇴

Bucharest, Romania

Spitalul Clinic Judeţean Mureş

🇷🇴

Târgu-Mureş, Romania

Hifu Terramed Conformal S.R.L

🇷🇴

Bucharest, Romania

Ankara Üniversitesi Tıp Fakültesi

🇹🇷

Ankara, Turkey

Ulsan University Hospital (UUH)

🇰🇷

Ulsan, Korea, Republic of

Centro Hospitalar do Porto, EPE - Hospital Geral de Santo António

🇵🇹

Porto, Portugal

Uludag Universitesi Tip Fakultesi, Uroloji Anabilim Dali, Gorukle

🇹🇷

Bursa, Turkey

Weill Cornell Medical College

🇺🇸

Denville, New Jersey, United States

Thomas Jefferson University Hospital

🇺🇸

Philadelphia, Pennsylvania, United States

UAB School of Medicine Spain Rehabilitation Center (SRC)

🇺🇸

Birmingham, Alabama, United States

Atlantic Urology Medical Group

🇺🇸

Long Beach, California, United States

Urological Associates of Southern Arizona, P.C.

🇺🇸

Tucson, Arizona, United States

UC Davis Medical Center

🇺🇸

Sacramento, California, United States

Women's Health Specialty Care

🇺🇸

Farmington, Connecticut, United States

University of Colorado Denver

🇺🇸

Aurora, Colorado, United States

Gousse Urology - The Bladder Heath and Reconstructive Urology Institute

🇺🇸

Miramar, Florida, United States

The Iowa Clinic, PC

🇺🇸

West Des Moines, Iowa, United States

Chesapeake Urology Associates, PA

🇺🇸

Owings Mills, Maryland, United States

University of Michigan Hospital

🇺🇸

Ann Arbor, Michigan, United States

Urology Group of New Mexico, PC

🇺🇸

Albuquerque, New Mexico, United States

University of North Carolina School of Medicine

🇺🇸

Chapel Hill, North Carolina, United States

New York University Langone Medical Center and School of Medicine

🇺🇸

New York, New York, United States

New York-Presbyterian Hospital/Weill Cornell Medical Center

🇺🇸

New York, New York, United States

Advanced Urology Centers of New York

🇺🇸

Plainview, New York, United States

Lancaster Urology

🇺🇸

Lancaster, Pennsylvania, United States

Levine Cancer Institute

🇺🇸

Charlotte, North Carolina, United States

Medical University of South Carolina (MUSC)

🇺🇸

Charleston, South Carolina, United States

Vanderbilt University Medical Center

🇺🇸

Nashville, Tennessee, United States

Houston Methodist Hospital

🇺🇸

Houston, Texas, United States

Lahey Hospital & Medical Center

🇺🇸

Burlington, Vermont, United States

Urology of Virginia, PLLC

🇺🇸

Virginia Beach, Virginia, United States

UBC Hospital - Koerner Pavilion

🇨🇦

Vancouver, Canada

CHUS - Hôpital Fleurimont

🇨🇦

Sherbrooke, Canada

Sunnybrook Health Sciences Centre

🇨🇦

Toronto, Canada

Integrity Medical Research

🇺🇸

Mountlake Terrace, Washington, United States

Medical College of Wisconsin - Freodert Hospital

🇺🇸

Milwaukee, Wisconsin, United States

Fakultní Nemocnice Brno

🇨🇿

Brno, Czechia

Spinal Cord Research Centre, University of Manitoba

🇨🇦

Winnipeg, Canada

Karlovarska krajska nemocnice, a.s.

🇨🇿

Karlovy Vary, Czechia

Uromedical Center s.r.o.

🇨🇿

Olomouc, Czechia

Ospedale "Bolognini" di Seriate

🇮🇹

Seriate, Italy

Všeobecná fakultní nemocnice v Praze

🇨🇿

Praha 2, Czechia

Krajská Nemocnice Liberec, a.s.

🇨🇿

Liberec, Czechia

Fakultní nemocnice Královské Vinohrady

🇨🇿

Praha 10, Czechia

Urologicka Ordinace s.r.o.

🇨🇿

Sternberk, Czechia

Azienda Ospedaliero-Universitaria Careggi - Dipartimento Di Neuro-Urologia

🇮🇹

Firenze, Italy

Azienda Ospedaliera di Perugia - Ospedale Santa Maria della Misericordia

🇮🇹

Udine, Italy

Thomayerova nemocnice

🇨🇿

Praha, Czechia

Fakultní Nemocnice v Motole

🇨🇿

Praha 5, Czechia

Farmacia Istituto Ospedaliero ICOT "Marco Pasquali"

🇮🇹

Latina, Italy

Viale Oxford, 81

🇮🇹

Roma, Italy

88 Olympic-ro 43-gil, Songpa-gu

🇰🇷

Seoul, Korea, Republic of

Samsung Medical Center

🇰🇷

Seoul, Korea, Republic of

Nzoz Neuro-Medic Poradnia Wielospecjalistyczna

🇵🇱

Katowice, Poland

Centro Hospitalar do Alto Ave, EPE

🇵🇹

Guimarães, Portugal

Gnosis Evomed

🇷🇴

Bucharest, Romania

Centro Hospitalar de São João, EPE - Hospital de São João

🇵🇹

Porto, Portugal

Spitalul Clinic Fundeni Bucureşti

🇷🇴

Bucharest, Romania

Medipol Mega University Hospital

🇹🇷

Bagcilar, Turkey

Marmara Üniversitesi Eğitim ve Araştırma Hastanesi

🇹🇷

Istanbul, Turkey

Istanbul Medeniyet Universitesi Goztepe Egitim ve Arastirma Hastanesi Merdivenköy Mah

🇹🇷

Istanbul, Turkey

Erciyes Üniversitesi Tıp Fakültesi

🇹🇷

Kayseri, Turkey

Kocaeli Üniversitesi Tıp Fakültesi

🇹🇷

Kocaeli, Turkey

Celal Bayar Universitesi Hafsa Sultan Hastanesi

🇹🇷

Manisa, Turkey

Ondokuz Mayıs Üniversitesi Tıp Fakültesi

🇹🇷

Samsun, Turkey

Montefiore Medical Center

🇺🇸

Bronx, New York, United States

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