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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 2

Phase 3
Terminated
Conditions
Urinary Incontinence
Overactive Bladder
Interventions
Biological: Botulinum toxin type A
Drug: Placebo
Registration Number
NCT02660359
Lead Sponsor
Ipsen
Brief Summary

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).

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
258
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
600 U Dysport® GroupBotulinum toxin type A-
600 U Dysport® Placebo GroupPlacebo-
800 U Dysport® GroupBotulinum toxin type A-
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 Detrusor Pressure (MDP) During Storage at Week 6 of DBPC CycleBaseline and 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.

Percentage 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. 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.

Percentage 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 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.

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.

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

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.

Median Time Between TreatmentsDay of first treatment (baseline) to 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 and subjects with no retreatment were censored at the last visit.

Mean Change From Baseline in Maximum Cystometric Capacity (MCC) at Week 6 of DBPC CycleBaseline and 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).

Percentage of Subjects With No Involuntary Detrusor Contraction (IDCs) During Storage at Week 6 of DBPC CycleBaseline and 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.

Trial Locations

Locations (82)

Asociacion IPS Medicos Internistas de Caldas

🇨🇴

Manizales, Colombia

Clínica Uromed

🇨🇱

Santiago, Chile

Solano & Terront Servicios Medicos LTDA- Unidad Integral de Endocrinologia

🇨🇴

Bogotá, Colombia

Centro Medico Puerta de Hierro - Colima

🇲🇽

Colima, Mexico

Instituto de Ginecología y Reproducción

🇵🇪

Lima, Peru

Kiev City Clinical Hospital No. 3

🇺🇦

Kiev, Ukraine

Hospital Privado - Centro Médico de Córdoba

🇦🇷

Córdoba, Argentina

Instituto Urológico Buenos Aires

🇦🇷

Buenos Aires, Argentina

Antwerp University hospital

🇧🇪

Antwerp, Belgium

Prince of Wales Hospital (POWH)

🇦🇺

Sydney, Australia

Universidade Estadual de Campinas - Cidade Universitária Zeferino Vaz

🇧🇷

Campinas, Brazil

Westmead Hospital

🇦🇺

Westmead, Australia

Hospital de Clinicas, Federal University of Paraná

🇧🇷

Curitiba, Brazil

Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

🇧🇷

Sao Paulo, Brazil

Centro Medico Imbanaco

🇨🇴

Cali, Colombia

Meir Medical Center

🇮🇱

Kfar Saba, Israel

Hôpital de la Conception

🇫🇷

Marseille CEDEX 5, France

Rambam Medical Center

🇮🇱

Haifa, Israel

Rabin Medical Center - Davidoff Center

🇮🇱

Petah Tikva, Israel

Scientific research institute of urology and interventional radiology n. a. N. A. Lopatkin

🇷🇺

Moscow, Russian Federation

Vilnius University Hospital Santariskiu Klinikos

🇱🇹

Vilnius, Lithuania

Consultorio Privado

🇲🇽

Zapopan, Mexico

Fundacio Puigvert

🇪🇸

Barcelona, Spain

Fundació GAEM

🇪🇸

Barcelona, Spain

Hospital Universitario Virgen del Rocío

🇪🇸

Sevilla, Spain

Royal National Orthopaedic Hospital Trust

🇬🇧

Stanmore, United Kingdom

Centro de Urologia

🇦🇷

Buenos Aires, Argentina

Hôpital Erasme

🇧🇪

Brussels, Belgium

Instituto Médico Rodriguez Alfici

🇦🇷

Godoy Cruz, Argentina

Ourthe-Amblève

🇧🇪

Esneux, Belgium

Hospital São Vicente de Paulo

🇧🇷

Passo Fundo, Brazil

Hospital São Lucas da PUCRS

🇧🇷

Pôrto Alegre, Brazil

Hospital Alemão Oswaldo Cruz

🇧🇷

São Paulo, Brazil

Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo

🇧🇷

Ribeirao Preto, Brazil

Clínica Las Condes

🇨🇱

Santiago, Chile

Fundación Valle del Lili

🇨🇴

Cali, Colombia

Centro de Investigaciones Clinicas - CIC

🇨🇴

Medellin, Colombia

Centre Hospitalier Régional Universitaire de Lille (CHRU) - Hôpital Claude Huriez

🇫🇷

Lille Cedex, France

Groupe Hospitalo-Universitaire Pierre Caremau

🇫🇷

Nimes Cedex 9, France

Hopital de la Source

🇫🇷

Orleans, France

Hôpital Tenon

🇫🇷

Paris Cedex 20, France

Hopital Pitie-Salpetriere

🇫🇷

Paris, France

CHU de Rennes - Hôpital Pontchaillou

🇫🇷

Rennes, France

Centre Hospitalier Lyon-Sud

🇫🇷

Pierre-Bénite, France

CHU de ROUEN - Hôpital Charles Nicolle

🇫🇷

Rouen Cedex, France

Hôpital Rangueil

🇫🇷

Toulouse Cedex 9, France

Kliniken Maria Hilf GmbH - Krankenhaus St. Franziskus

🇩🇪

Monchengladbach, Germany

Universitätsklinikum Münster

🇩🇪

Münster, Germany

Carmel Medical Center

🇮🇱

Haifa, Israel

The Chaim Sheba Medical Center

🇮🇱

Ramat Gan, Israel

Estetines Chirurgijos Centas, UAB

🇱🇹

Kaunas, Lithuania

Clinica Internacional Sede Lima

🇵🇪

Lima, Peru

Hospital Universitario "Dr. José Eleuterio González"

🇲🇽

Monterrey, Mexico

Clínica San Pablo Surco

🇵🇪

Lima, Peru

Clinstile, S.A. de C.V.

🇲🇽

Cuauhtémoc, Mexico

Clinica Good Hope

🇵🇪

Lima, Peru

Clínica Anglo Americana

🇵🇪

Lima, Peru

Ministry of healthcare of the Russian Federation

🇷🇺

Moscow, Russian Federation

Unidad de Investigación de la Clínica Internacional Sede San Borja

🇵🇪

Lima, Peru

Rostov State Medical University

🇷🇺

Rostov-on-Don, Russian Federation

Hospital Orkli

🇷🇺

Saint Petersburg, Russian Federation

Complexo Hospitalario Universitario A Coruña

🇪🇸

A Coruña, Spain

St. Petersburg Research Institute of Phthisiopulmonology

🇷🇺

Saint Petersburg, Russian Federation

City Hospital No. 40

🇷🇺

Saint Petersburg, Russian Federation

Hospital Universitario Vall d'Hebron

🇪🇸

Barcelona, Spain

Hospital Universitari i Politècnic La Fe

🇪🇸

Valencia, Spain

Hospital Universitario La Paz

🇪🇸

Madrid, Spain

National Hospital for Neurology and Neurosurgery - UCL

🇬🇧

London, United Kingdom

Bedford Hospital

🇬🇧

Bedford, United Kingdom

Sheffield Teaching Hospitals NHS Foundation Trust - Royal Hallamshire Hospital

🇬🇧

Sheffield, United Kingdom

The Mid Yorkshire Hospitals NHS Trust - Pinderfields Hospital

🇬🇧

Wakefield, United Kingdom

Centro Urológico Profesor Bengió

🇦🇷

Córdoba, Argentina

Hospital Moinhos de Vento

🇧🇷

Pôrto Alegre, Brazil

Hôpital Raymond-Poincaré

🇫🇷

Garches, France

Faculdade de Medicina do ABC

🇧🇷

Santo André, Brazil

Universitätsklinikum Bonn Klinik und Poliklinik für Urologie

🇩🇪

Bonn, Germany

Santa Casa de Misericórdia de Porto Alegre - Hospital Santa Clara

🇧🇷

Porto Alegre, Brazil

Penza Regional Clinical Hospital n.a. N.N.Burdenko

🇷🇺

Penza, Russian Federation

Pavlov First Saint Petersburg State Medical University

🇷🇺

Saint Petersburg, Russian Federation

NHS Grampian - Aberdeen Royal Infirmary

🇬🇧

Aberdeen, United Kingdom

Hospital del Trabajador

🇨🇱

Santiago, Chile

Municipal Healthcare Institution "Regional Clinical Center of Urology and Nephrology n.a. V.I. Shapoval", Urology Department

🇺🇦

Kharkiv, Ukraine

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