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

Urinary Incontinence Clinical Trial

— CONTENT2  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02660359
• Other study ID #: D-FR-52120-223
• Secondary ID: 2015-000507-44
• Status: Terminated
• Phase: Phase 3
• Start date: July 8, 2016
• Est. completion date: July 4, 2019

Study information

• Verified date: September 2022
• Source: Ipsen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 258
• Est. completion date: July 4, 2019
• Est. primary completion date: November 9, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Enuresis
• Multiple Sclerosis
• Overactive Bladder
• Spinal Cord Injuries
• Urinary Bladder, Overactive
• Urinary Incontinence

Intervention

Biological:
• Botulinum toxin type A
600 U intra detrusor injection in two treatment periods (Initial and Retreatment phase) delivered at 30 injection points.
• Botulinum toxin type A
800 U intra detrusor injection in two treatment periods (Initial and Retreatment phase) delivered at 30 injection points

Drug:
• Placebo
AbobotulinumtoxinA Placebo 600 U intra detrusor injection in two treatment periods (Initial and Retreatment phase) delivered at 30 injection points
• Placebo
AbobotulinumtoxinA Placebo 800 U intra detrusor injection in two treatment periods (Initial and Retreatment phase) delivered at 30 injection points

Locations

Country	Name	City	State
Argentina	Centro de Urologia	Buenos Aires
Argentina	Instituto Urológico Buenos Aires	Buenos Aires
Argentina	Centro Urológico Profesor Bengió	Córdoba
Argentina	Hospital Privado - Centro Médico de Córdoba	Córdoba
Argentina	Instituto Médico Rodriguez Alfici	Godoy Cruz
Australia	Prince of Wales Hospital (POWH)	Sydney
Australia	Westmead Hospital	Westmead
Belgium	Antwerp University hospital	Antwerp
Belgium	Hôpital Erasme	Brussels
Belgium	Ourthe-Amblève	Esneux
Brazil	Universidade Estadual de Campinas - Cidade Universitária Zeferino Vaz	Campinas
Brazil	Hospital de Clinicas, Federal University of Paraná	Curitiba
Brazil	Hospital São Vicente de Paulo	Passo Fundo
Brazil	Santa Casa de Misericórdia de Porto Alegre - Hospital Santa Clara	Porto Alegre
Brazil	Hospital Moinhos de Vento	Pôrto Alegre
Brazil	Hospital São Lucas da PUCRS	Pôrto Alegre
Brazil	Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo	Ribeirao Preto
Brazil	Faculdade de Medicina do ABC	Santo André
Brazil	Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo	Sao Paulo
Brazil	Hospital Alemão Oswaldo Cruz	São Paulo
Chile	Clínica Las Condes	Santiago
Chile	Clínica Uromed	Santiago
Chile	Hospital del Trabajador	Santiago
Colombia	Solano & Terront Servicios Medicos LTDA- Unidad Integral de Endocrinologia	Bogotá
Colombia	Centro Medico Imbanaco	Cali
Colombia	Fundación Valle del Lili	Cali
Colombia	Asociacion IPS Medicos Internistas de Caldas	Manizales
Colombia	Centro de Investigaciones Clinicas - CIC	Medellin
France	Hôpital Raymond-Poincaré	Garches
France	Centre Hospitalier Régional Universitaire de Lille (CHRU) - Hôpital Claude Huriez	Lille Cedex
France	Hôpital de la Conception	Marseille CEDEX 5
France	Groupe Hospitalo-Universitaire Pierre Caremau	Nimes Cedex 9
France	Hopital de la Source	Orleans
France	Hopital Pitie-Salpetriere	Paris
France	Hôpital Tenon	Paris Cedex 20
France	Centre Hospitalier Lyon-Sud	Pierre-Bénite
France	CHU de Rennes - Hôpital Pontchaillou	Rennes
France	CHU de ROUEN - Hôpital Charles Nicolle	Rouen Cedex
France	Hôpital Rangueil	Toulouse Cedex 9
Germany	Universitätsklinikum Bonn Klinik und Poliklinik für Urologie	Bonn
Germany	Kliniken Maria Hilf GmbH - Krankenhaus St. Franziskus	Monchengladbach
Germany	Universitätsklinikum Münster	Münster
Israel	Carmel Medical Center	Haifa
Israel	Rambam Medical Center	Haifa
Israel	Meir Medical Center	Kfar Saba
Israel	Rabin Medical Center - Davidoff Center	Petah Tikva
Israel	The Chaim Sheba Medical Center	Ramat Gan
Lithuania	Estetines Chirurgijos Centas, UAB	Kaunas
Lithuania	Vilnius University Hospital Santariskiu Klinikos	Vilnius
Mexico	Centro Medico Puerta de Hierro - Colima	Colima
Mexico	Clinstile, S.A. de C.V.	Cuauhtémoc
Mexico	Hospital Universitario "Dr. José Eleuterio González"	Monterrey
Mexico	Consultorio Privado	Zapopan
Peru	Clínica Anglo Americana	Lima
Peru	Clinica Good Hope	Lima
Peru	Clinica Internacional Sede Lima	Lima
Peru	Clínica San Pablo Surco	Lima
Peru	Instituto de Ginecología y Reproducción	Lima
Peru	Unidad de Investigación de la Clínica Internacional Sede San Borja	Lima
Russian Federation	Ministry of healthcare of the Russian Federation	Moscow
Russian Federation	Scientific research institute of urology and interventional radiology n. a. N. A. Lopatkin	Moscow
Russian Federation	Penza Regional Clinical Hospital n.a. N.N.Burdenko	Penza
Russian Federation	Rostov State Medical University	Rostov-on-Don
Russian Federation	City Hospital No. 40	Saint Petersburg
Russian Federation	Hospital Orkli	Saint Petersburg
Russian Federation	Pavlov First Saint Petersburg State Medical University	Saint Petersburg
Russian Federation	St. Petersburg Research Institute of Phthisiopulmonology	Saint Petersburg
Spain	Complexo Hospitalario Universitario A Coruña	A Coruña
Spain	Fundació GAEM	Barcelona
Spain	Fundacio Puigvert	Barcelona
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Virgen del Rocío	Sevilla
Spain	Hospital Universitari i Politècnic La Fe	Valencia
Ukraine	Municipal Healthcare Institution "Regional Clinical Center of Urology and Nephrology n.a. V.I. Shapoval", Urology Department	Kharkiv
Ukraine	Kiev City Clinical Hospital No. 3	Kiev
United Kingdom	NHS Grampian - Aberdeen Royal Infirmary	Aberdeen
United Kingdom	Bedford Hospital	Bedford
United Kingdom	National Hospital for Neurology and Neurosurgery - UCL	London
United Kingdom	Sheffield Teaching Hospitals NHS Foundation Trust - Royal Hallamshire Hospital	Sheffield
United Kingdom	Royal National Orthopaedic Hospital Trust	Stanmore
United Kingdom	The Mid Yorkshire Hospitals NHS Trust - Pinderfields Hospital	Wakefield

Sponsors (1)

Lead Sponsor	Collaborator
Ipsen

Countries where clinical trial is conducted

Argentina,  Australia,  Belgium,  Brazil,  Chile,  Colombia,  France,  Germany,  Israel,  Lithuania,  Mexico,  Peru,  Russian Federation,  Spain,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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