Dysport® Treatment of Urinary Incontinence in Adults Subjects With Neurogenic Detrusor Overactivity (NDO) Due to Spinal Cord Injury or Multiple Sclerosis - Study 1 (CONTENT1)

A Phase III, Multicentre, Randomised, Double Blind, Parallel Group, Placebo Controlled Study To Assess The Efficacy And Safety Of One Or More Intradetrusor Treatments Of 600 Or 800 Units of Dysport® For The Treatment Of Urinary Incontinence In Subjects With Neurogenic Detrusor Overactivity Due To Spinal Cord Injury Or Multiple Sclerosis

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).

Study Overview

• Status: Terminated
• Conditions: Overactive Bladder; Urinary Incontinence
• Intervention / Treatment: Biological: Botulinum toxin type A; Drug: Placebo; Drug: Placebo; Biological: Botulinum toxin type A

• Study Type: Interventional
• Enrollment (Actual): 227
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Sherbrooke, Canada, 02114-2621
    • CHUS - Hôpital Fleurimont
  • Toronto, Canada, 02115-6110
    • Sunnybrook Health Sciences Centre
  • Vancouver, Canada, V6T 2B5
    • UBC Hospital - Koerner Pavilion
  • Winnipeg, Canada, R3A 1M4
    • Spinal Cord Research Centre, University of Manitoba
• Czechia
  • Brno, Czechia, 62500
    • Fakultni nemocnice Brno
  • Karlovy Vary, Czechia, 360 01
    • Karlovarska krajska nemocnice, a.s.
  • Liberec, Czechia, 46063
    • Krajska nemocnice Liberec, a.s.
  • Olomouc, Czechia, 77900
    • Uromedical Center s.r.o.
  • Praha, Czechia, 14059
    • Thomayerova nemocnice
  • Praha 10, Czechia, 100 34
    • Fakultni nemocnice Kralovske Vinohrady
  • Praha 2, Czechia, 12808
    • Vseobecna fakultni nemocnice v Praze
  • Praha 5, Czechia, 15006
    • Fakultni nemocnice v Motole
  • Sternberk, Czechia, 785 01
    • Urologicka Ordinace s.r.o.
• Italy
  • Firenze, Italy, 50134
    • Azienda Ospedaliero-Universitaria Careggi - Dipartimento Di Neuro-Urologia
  • Latina, Italy, 04100
    • Farmacia Istituto Ospedaliero ICOT "Marco Pasquali"
  • Perugia, Italy, 06132
    • Azienda Ospedaliera di Perugia - Ospedale Santa Maria della Misericordia
  • Roma, Italy, 00133
    • Viale Oxford, 81
  • Seriate, Italy, 24068
    • Ospedale "Bolognini" di Seriate
  • Udine, Italy, 33100
    • Azienda Ospedaliera di Perugia - Ospedale Santa Maria della Misericordia
• Korea, Republic of
  • Seoul, Korea, Republic of, 6351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 05505
    • 88 Olympic-ro 43-gil, Songpa-gu
  • Ulsan, Korea, Republic of, 44033
    • Ulsan University Hospital (UUH)
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • VU University Medical Center
  • Nijmegen, Netherlands, 6525 GA
    • Radboud UMC
  • Rotterdam, Netherlands, 3015 CE
    • Erasmus MC
• Poland
  • Elblag, Poland, 82-300
    • Wojewodzki Szpital Zespolony w Elblagu
  • Katowice, Poland, 40-752
    • Nzoz Neuro-Medic Poradnia Wielospecjalistyczna
  • Piaseczno, Poland, 05-500
    • NZOZ Heureka
  • Warszawa, Poland, 02-005
    • Szpital Kliniczny Dzieciątka Jezus w Warszawie
  • Wroclaw, Poland, 54-144
    • EuroMediCare Szpital Specjalistyczny z Przychodnią we Wrocławiu
• Portugal
  • Braga, Portugal, 4700-001
    • Hospital de Braga
  • Guimarães, Portugal, 4835-044
    • Centro Hospitalar Do Alto Ave, Epe
  • Lisboa, Portugal, 1600-209
    • British Hospital
  • Porto, Portugal, 4200-319
    • Centro Hospitalar de São João, EPE - Hospital de São João
  • Porto, Portugal, 4099-001
    • Centro Hospitalar do Porto, EPE - Hospital Geral de Santo António
• Romania
  • Bucharest, Romania, 20125
    • Spitalul Clinic Colentina
  • Bucharest, Romania, 031864
    • Gnosis Evomed
  • Bucharest, Romania, 22328
    • Spitalul Clinic Fundeni Bucureşti
  • Bucharest, Romania, 31864
    • Hifu Terramed Conformal S.R.L
  • Târgu-Mureş, Romania, 540103
    • Spitalul Clinic Judetean Mures
• Turkey
  • Ankara, Turkey, 6100
    • Ankara Üniversitesi Tıp Fakültesi
  • Bagcilar, Turkey, 34200
    • Medipol Mega University Hospital
  • Bursa, Turkey, 16059
    • Uludag Universitesi Tip Fakultesi, Uroloji Anabilim Dali, Gorukle
  • Istanbul, Turkey, 34670
    • Marmara Üniversitesi Eğitim ve Araştırma Hastanesi
  • Istanbul, Turkey, 34732
    • Istanbul Medeniyet Universitesi Goztepe Egitim ve Arastirma Hastanesi Merdivenköy Mah
  • Kayseri, Turkey, 38039
    • Erciyes Üniversitesi Tıp Fakültesi
  • Kocaeli, Turkey, 41380
    • Kocaeli Üniversitesi Tıp Fakültesi
  • Manisa, Turkey, 45040
    • Celal Bayar Universitesi Hafsa Sultan Hastanesi
  • Samsun, Turkey, 55139
    • Ondokuz Mayıs Universitesi Tıp Fakültesi
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • UAB School of Medicine Spain Rehabilitation Center (SRC)
  • Arizona
    • Tucson, Arizona, United States, 85715-3808
      • Urological Associates of Southern Arizona, P.C.
  • California
    • Long Beach, California, United States, 90806
      • Atlantic Urology Medical Group
    • Los Angeles, California, United States, 90089
      • USC Norris Comprehensive Cancer Center
    • Sacramento, California, United States, 95817-2307
      • UC Davis Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045-2527
      • University of Colorado Denver
  • Connecticut
    • Farmington, Connecticut, United States, 06032-1933
      • Women's Health Specialty Care
  • Florida
    • Miramar, Florida, United States, 33029-5593
      • Gousse Urology - The Bladder Heath and Reconstructive Urology Institute
  • Iowa
    • West Des Moines, Iowa, United States, 50266
      • The Iowa Clinic, PC
  • Maryland
    • Owings Mills, Maryland, United States, 21117
      • Chesapeake Urology Associates, PA
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Hospital
  • New Jersey
    • Denville, New Jersey, United States, 07834
      • Weill Cornell Medical College
    • Voorhees, New Jersey, United States, 08043
      • Delaware Valley Urology,IIC
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Urology Group of New Mexico, PC
  • New York
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center
    • New York, New York, United States, 10065
      • New York-Presbyterian Hospital/Weill Cornell Medical Center
    • New York, New York, United States, 10016
      • New York University Langone Medical Center and School of Medicine
    • Plainview, New York, United States, 11783
      • Advanced Urology Centers of New York
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina School of Medicine
    • Charlotte, North Carolina, United States, 28207
      • Levine Cancer Institute
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Cleveland, Ohio, United States, 44106
      • Louis Stokes Cleveland Veterans Affairs Medical Center
  • Pennsylvania
    • Lancaster, Pennsylvania, United States, 17601
      • Lancaster Urology
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina (MUSC)
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75231
      • Urology Clinics of North Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
  • Vermont
    • Burlington, Vermont, United States, 01805-0001
      • Lahey Hospital & Medical Center
  • Virginia
    • Virginia Beach, Virginia, United States, 23462-1815
      • Urology Of Virginia, Pllc
  • Washington
    • Mountlake Terrace, Washington, United States, 98043
      • Integrity Medical Research
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin - Freodert Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key 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 Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 600 U Dysport® Group	Biological: Botulinum toxin type A; 800 U intra detrusor injection in two treatment periods (Initial and Retreatment phase) delivered at 30 injection points; Other Names: AbobotulinumtoxinA (Dysport®); Clostridium BTX-A-haemagglutinin complex; Biological: Botulinum toxin type A; 600 U intra detrusor injection in two treatment periods (Initial and Retreatment phase) delivered at 30 injection points; Other Names: AbobotulinumtoxinA (Dysport®); Clostridium BTX-A-haemagglutinin complex
PLACEBO_COMPARATOR: 600 U Dysport® Placebo Group	Drug: Placebo; AbobotulinumtoxinA Placebo 600 U intra detrusor injection in two treatment periods (Initial and Retreatment phase) delivered at 30 injection points; Drug: Placebo; AbobotulinumtoxinA Placebo 800 U intra detrusor injection in two treatment periods (Initial and Retreatment phase) delivered at 30 injection points
EXPERIMENTAL: 800 U Dysport® Group	Biological: Botulinum toxin type A; 800 U intra detrusor injection in two treatment periods (Initial and Retreatment phase) delivered at 30 injection points; Other Names: AbobotulinumtoxinA (Dysport®); Clostridium BTX-A-haemagglutinin complex; Biological: Botulinum toxin type A; 600 U intra detrusor injection in two treatment periods (Initial and Retreatment phase) delivered at 30 injection points; Other Names: AbobotulinumtoxinA (Dysport®); Clostridium BTX-A-haemagglutinin complex
PLACEBO_COMPARATOR: 800 U Dysport® Placebo Group	Drug: Placebo; AbobotulinumtoxinA Placebo 600 U intra detrusor injection in two treatment periods (Initial and Retreatment phase) delivered at 30 injection points; Drug: Placebo; AbobotulinumtoxinA Placebo 800 U intra detrusor injection in two treatment periods (Initial and Retreatment phase) delivered at 30 injection points

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in Weekly Number of UI Episodes at 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.	Baseline and Week 6 of DBPC Cycle

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in Volume Per Void at 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.	Baseline and Week 6 of DBPC Cycle
Mean Change From Baseline in Maximum Cystometric Capacity (MCC) at 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).	Baseline and Week 6 of DBPC Cycle
Mean Change From Baseline in Maximum Detrusor Pressure (MDP) at 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.	Baseline and Week 6 of DBPC Cycle
Mean Change From Baseline in Volume at First Involuntary Detrusor Contraction (Vol@1stIDC) at 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.	Baseline and Week 6 of DBPC Cycle
Number of Subjects With No Episodes of UI at 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.	Baseline and Week 6 of DBPC Cycle
Number of Subjects With No IDCs During Storage at 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.	Baseline and Week 6 of DBPC Cycle
Mean Change From Baseline in Incontinence Quality of Life (I-QoL) Questionnaire Total Summary Score at 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.	Baseline and Week 6 of DBPC Cycle
Number of Subjects With a UI Response at Improvement Levels ≥30%, ≥50%, and ≥75% at Week 6 of the 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.	Baseline and Week 6 of DBPC Cycle
Median Time Between Treatments	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.	Day of first treatment (baseline) and day of retreatment, up to 2 years

Collaborators and Investigators

• Sponsor: Ipsen

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (ACTUAL): November 9, 2018
• Study Completion (ACTUAL): February 14, 2019

Study Registration Dates

• First Submitted: January 14, 2016
• First Submitted That Met QC Criteria: January 18, 2016
• First Posted (ESTIMATE): January 21, 2016

Study Record Updates

• Last Update Posted (ACTUAL): September 28, 2022
• Last Update Submitted That Met QC Criteria: September 15, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Central Nervous System Diseases; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Urologic Diseases; Urinary Bladder Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Wounds and Injuries; Urination Disorders; Trauma, Nervous System; Spinal Cord Diseases; Elimination Disorders; Multiple Sclerosis; Urinary Bladder, Overactive; Urinary Incontinence; Spinal Cord Injuries; Enuresis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Immunologic Factors; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Agglutinins; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA; Hemagglutinins
• Other Study ID Numbers: D-FR-52120-222; 2015-003471-30 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized, and study documents will be redacted to protect the privacy of study participants.

Any requests should be submitted to www.vivli.org for assessment by an independent scientific review board.

• IPD Sharing Time Frame: Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the US and EU or after the primary manuscript describing the results has been accepted for publication, whichever is later.
• IPD Sharing Access Criteria: Further details on Ipsen's sharing criteria, eligible studies and process for sharing are available here (https://vivli.org/members/ourmembers/).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No