Dysport® Treatment of Urinary Incontinence in Adults Subjects With Neurogenic Detrusor Overactivity (NDO) Due to Spinal Cord Injury or Multiple Sclerosis - Study 2 (CONTENT2)

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® 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; Biological: Botulinum toxin type A; Drug: Placebo; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 258
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1060
    • Instituto Urológico Buenos Aires
  • Buenos Aires, Argentina, C1120AAS
    • Centro de Urologia
  • Córdoba, Argentina, X5000
    • Centro Urologico Profesor Bengio
  • Córdoba, Argentina, X5016KEH
    • Hospital Privado - Centro Medico de Cordoba
  • Godoy Cruz, Argentina, M5501AAP
    • Instituto Médico Rodriguez Alfici
• Australia
  • Sydney, Australia, 2031
    • Prince of Wales Hospital (POWH)
  • Westmead, Australia, 2145
    • Westmead Hospital
• Belgium
  • Antwerp, Belgium
    • Antwerp University Hospital
  • Brussels, Belgium, 1070
    • Hopital Erasme
  • Esneux, Belgium, 4130
    • Ourthe-Amblève
• Brazil
  • Campinas, Brazil, 13083-970
    • Universidade Estadual de Campinas - Cidade Universitária Zeferino Vaz
  • Curitiba, Brazil, 80060-900
    • Hospital de Clinicas, Federal University of Paraná
  • Passo Fundo, Brazil, 99010-080
    • Hospital Sao Vicente de Paulo
  • Porto Alegre, Brazil, 90020-090
    • Santa Casa de Misericórdia de Porto Alegre - Hospital Santa Clara
  • Pôrto Alegre, Brazil, 90560-030
    • Hospital Moinhos de Vento
  • Pôrto Alegre, Brazil, 90610-000
    • Hospital Sao Lucas da PUCRS
  • Ribeirao Preto, Brazil, 14048-900
    • Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo
  • Santo André, Brazil, 09060-650
    • Faculdade de Medicina do ABC
  • Sao Paulo, Brazil, 05422-970
    • Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo
  • São Paulo, Brazil, 01323-020
    • Hospital Alemao Oswaldo Cruz
• Chile
  • Santiago, Chile, 7591046
    • Clinica Las Condes
  • Santiago, Chile, 7500787
    • Clínica Uromed
  • Santiago, Chile, 7501241
    • Hospital del Trabajador
• Colombia
  • Bogotá, Colombia, 110221
    • Solano & Terront Servicios Medicos LTDA- Unidad Integral de Endocrinologia
  • Cali, Colombia, 760032
    • Fundacion Valle del Lili
  • Cali, Colombia, 760042
    • Centro Medico Imbanaco
  • Manizales, Colombia, 170004
    • Asociacion IPS Medicos Internistas de Caldas
  • Medellin, Colombia, 5001000
    • Centro de Investigaciones Clinicas - CIC
• France
  • Garches, France
    • Hôpital Raymond-Poincaré
  • Lille Cedex, France
    • Centre Hospitalier Régional Universitaire de Lille (CHRU) - Hôpital Claude Huriez
  • Marseille CEDEX 5, France
    • Hôpital de la Conception
  • Nimes Cedex 9, France
    • Groupe Hospitalo-Universitaire Pierre Caremau
  • Orleans, France
    • Hôpital de la Source
  • Paris, France
    • Hôpital Pitié-Salpétrière
  • Paris Cedex 20, France
    • Hopital Tenon
  • Pierre-Bénite, France
    • Centre hospitalier Lyon-Sud
  • Rennes, France
    • CHU de Rennes - Hôpital Pontchaillou
  • Rouen Cedex, France
    • CHU de Rouen - Hôpital Charles Nicolle
  • Toulouse Cedex 9, France
    • Hopital Rangueil
• Germany
  • Bonn, Germany, 53127
    • Universitätsklinikum Bonn Klinik und Poliklinik für Urologie
  • Monchengladbach, Germany
    • Kliniken Maria Hilf GmbH - Krankenhaus St. Franziskus
  • Münster, Germany, 48149
    • Universitätsklinikum Münster
• Israel
  • Haifa, Israel, 31096
    • Rambam Medical Center
  • Haifa, Israel, 34362
    • Carmel Medical Center
  • Kfar Saba, Israel, 44281
    • Meir Medical Center
  • Petah Tikva, Israel, 49100
    • Rabin Medical Center - Davidoff Center
  • Ramat Gan, Israel, 52621
    • The Chaim Sheba Medical Center
• Lithuania
  • Kaunas, Lithuania, 49476
    • Estetines Chirurgijos Centas, UAB
  • Vilnius, Lithuania, 8661
    • Vilnius University Hospital Santariskiu Klinikos
• Mexico
  • Colima, Mexico, 28018
    • Centro Medico Puerta de Hierro - Colima
  • Cuauhtémoc, Mexico, 06700
    • Clinstile, S.A. de C.V.
  • Monterrey, Mexico, 64460
    • Hospital Universitario "Dr. Jose Eleuterio Gonzalez"
  • Zapopan, Mexico, 45040
    • Consultorio Privado
• Peru
  • Lima, Peru, 15023
    • Clínica San Pablo Surco
  • Lima, Peru, Lima18
    • Clinica Good Hope
  • Lima, Peru, Lima1
    • Clinica Internacional Sede Lima
  • Lima, Peru, Lima27
    • Clinica Anglo Americana
  • Lima, Peru, Lima33
    • Instituto de Ginecología y Reproducción
  • Lima, Peru, Lima41
    • Unidad de Investigación de la Clínica Internacional Sede San Borja
• Russian Federation
  • Moscow, Russian Federation, 105425
    • Scientific research institute of urology and interventional radiology n. a. N. A. Lopatkin
  • Moscow, Russian Federation, 129226
    • Ministry of healthcare of the Russian Federation
  • Penza, Russian Federation, 440026
    • Penza Regional Clinical Hospital n.a. N.N.Burdenko
  • Rostov-on-Don, Russian Federation, 344022
    • Rostov State Medical University
  • Saint Petersburg, Russian Federation, 194064
    • St. Petersburg Research Institute of Phthisiopulmonology
  • Saint Petersburg, Russian Federation, 197089
    • Pavlov First Saint Petersburg State Medical University
  • Saint Petersburg, Russian Federation, 197706
    • City Hospital No. 40
  • Saint Petersburg, Russian Federation
    • Hospital Orkli
• Spain
  • A Coruña, Spain
    • Complexo Hospitalario Universitario A Coruña
  • Barcelona, Spain, 08025
    • Fundacio Puigvert
  • Barcelona, Spain
    • Hospital Universitario Vall d'Hebron
  • Barcelona, Spain
    • Fundació GAEM
  • Madrid, Spain
    • Hospital Universitario La Paz
  • Sevilla, Spain
    • Hospital Universitario Virgen del Rocio
  • Valencia, Spain
    • Hospital Universitari i Politecnic La Fe
• Ukraine
  • Kharkiv, Ukraine, 61037
    • Municipal Healthcare Institution "Regional Clinical Center of Urology and Nephrology n.a. V.I. Shapoval", Urology Department
  • Kiev, Ukraine, 02125
    • Kiev City Clinical Hospital No. 3
• United Kingdom
  • Aberdeen, United Kingdom, AB25 2ZN
    • NHS Grampian - Aberdeen Royal Infirmary
  • Bedford, United Kingdom, MK42 9DJ
    • Bedford Hospital
  • London, United Kingdom, WC1N 3BG
    • National Hospital for Neurology and Neurosurgery - UCL
  • Sheffield, United Kingdom, S10 2JF
    • Sheffield Teaching Hospitals NHS Foundation Trust - Royal Hallamshire Hospital
  • Stanmore, United Kingdom, HA7 4LP
    • Royal National Orthopaedic Hospital Trust
  • Wakefield, United Kingdom, WF1 4DG
    • The Mid Yorkshire Hospitals NHS Trust - Pinderfields 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; 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; 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
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; 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; 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
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
Percentage 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. Percentage of subjects with no episodes of UI (≥100% Improvement) was calculated as: Total number of subjects with no weekly number of UI episodes at Week 6 / Total number of subjects with any number of UI events at Week 6.	Baseline and Week 6 of DBPC Cycle
Percentage 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 percentage of subjects showing an improvement of ≥30%, ≥50% and ≥75% was calculated as: Total number of subjects with UI response level >=30% or >=50% or >=75% improvement at Week 6 / Total number of subjects with any UI response 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 and subjects with no retreatment were censored at the last visit.	Day of first treatment (baseline) to day of retreatment, up to 2 years
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	Subjects included in the urodynamic subset (84.9% of randomised 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) During Storage at Week 6 of DBPC Cycle	Subjects included in the urodynamic subset (84.9% of randomised 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	Subjects included in the urodynamic subset (84.9% of randomised 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
Percentage of Subjects With No Involuntary Detrusor Contraction (IDCs) During Storage at Week 6 of DBPC Cycle	Subjects included in the urodynamic subset (84.9% of randomised subjects) had a standardised urodynamic filling cystometry assessment at baseline (Screening) and again at Week 6 to determine the occurrence of IDCs. The percentage of subjects without IDCs at 6 weeks after the first study treatment was recorded.	Baseline and Week 6 of DBPC Cycle

Collaborators and Investigators

• Sponsor: Ipsen

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 8, 2016
• Primary Completion (ACTUAL): November 9, 2018
• Study Completion (ACTUAL): July 4, 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-52120-223; 2015-000507-44 (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