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

Urinary Incontinence Clinical Trial

— CONTENT1  

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: NCT02660138
• Other study ID #: D-FR-52120-222
• Secondary ID: 2015-003471-30
• Status: Terminated
• Phase: Phase 3
• Start date: March 2016
• Est. completion date: February 14, 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® (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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 227
• Est. completion date: February 14, 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
Canada	CHUS - Hôpital Fleurimont	Sherbrooke
Canada	Sunnybrook Health Sciences Centre	Toronto
Canada	UBC Hospital - Koerner Pavilion	Vancouver
Canada	Spinal Cord Research Centre, University of Manitoba	Winnipeg
Czechia	Fakultní Nemocnice Brno	Brno
Czechia	Karlovarska krajska nemocnice, a.s.	Karlovy Vary
Czechia	Krajská Nemocnice Liberec, a.s.	Liberec
Czechia	Uromedical Center s.r.o.	Olomouc
Czechia	Thomayerova nemocnice	Praha
Czechia	Fakultní nemocnice Královské Vinohrady	Praha 10
Czechia	Všeobecná fakultní nemocnice v Praze	Praha 2
Czechia	Fakultní Nemocnice v Motole	Praha 5
Czechia	Urologicka Ordinace s.r.o.	Sternberk
Italy	Azienda Ospedaliero-Universitaria Careggi - Dipartimento Di Neuro-Urologia	Firenze
Italy	Farmacia Istituto Ospedaliero ICOT "Marco Pasquali"	Latina
Italy	Azienda Ospedaliera di Perugia - Ospedale Santa Maria della Misericordia	Perugia
Italy	Viale Oxford, 81	Roma
Italy	Ospedale "Bolognini" di Seriate	Seriate
Italy	Azienda Ospedaliera di Perugia - Ospedale Santa Maria della Misericordia	Udine
Korea, Republic of	88 Olympic-ro 43-gil, Songpa-gu	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Ulsan University Hospital (UUH)	Ulsan
Netherlands	VU University Medical Center	Amsterdam
Netherlands	Radboud UMC	Nijmegen
Netherlands	Erasmus MC	Rotterdam
Poland	Wojewódzki Szpital Zespolony w Elblagu	Elblag
Poland	Nzoz Neuro-Medic Poradnia Wielospecjalistyczna	Katowice
Poland	NZOZ Heureka	Piaseczno
Poland	Szpital Kliniczny Dzieciatka Jezus w Warszawie	Warszawa
Poland	EuroMediCare Szpital Specjalistyczny z Przychodnia we Wroclawiu	Wroclaw
Portugal	Hospital de Braga	Braga
Portugal	Centro Hospitalar do Alto Ave, EPE	Guimarães
Portugal	British Hospital	Lisboa
Portugal	Centro Hospitalar de São João, EPE - Hospital de São João	Porto
Portugal	Centro Hospitalar do Porto, EPE - Hospital Geral de Santo António	Porto
Romania	Gnosis Evomed	Bucharest
Romania	Hifu Terramed Conformal S.R.L	Bucharest
Romania	Spitalul Clinic Colentina	Bucharest
Romania	Spitalul Clinic Fundeni Bucuresti	Bucharest
Romania	Spitalul Clinic Judetean Mures	Târgu-Mures
Turkey	Ankara Üniversitesi Tip Fakültesi	Ankara
Turkey	Medipol Mega University Hospital	Bagcilar
Turkey	Uludag Universitesi Tip Fakultesi, Uroloji Anabilim Dali, Gorukle	Bursa
Turkey	Istanbul Medeniyet Universitesi Goztepe Egitim ve Arastirma Hastanesi Merdivenköy Mah	Istanbul
Turkey	Marmara Üniversitesi Egitim ve Arastirma Hastanesi	Istanbul
Turkey	Erciyes Üniversitesi Tip Fakültesi	Kayseri
Turkey	Kocaeli Üniversitesi Tip Fakültesi	Kocaeli
Turkey	Celal Bayar Universitesi Hafsa Sultan Hastanesi	Manisa
Turkey	Ondokuz Mayis Üniversitesi Tip Fakültesi	Samsun
United States	Urology Group of New Mexico, PC	Albuquerque	New Mexico
United States	University of Michigan Hospital	Ann Arbor	Michigan
United States	University of Colorado Denver	Aurora	Colorado
United States	UAB School of Medicine Spain Rehabilitation Center (SRC)	Birmingham	Alabama
United States	Montefiore Medical Center	Bronx	New York
United States	Lahey Hospital & Medical Center	Burlington	Vermont
United States	University of North Carolina School of Medicine	Chapel Hill	North Carolina
United States	Medical University of South Carolina (MUSC)	Charleston	South Carolina
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	Cleveland Clinic	Cleveland	Ohio
United States	Louis Stokes Cleveland Veterans Affairs Medical Center	Cleveland	Ohio
United States	Urology Clinics of North Texas	Dallas	Texas
United States	Weill Cornell Medical College	Denville	New Jersey
United States	Women's Health Specialty Care	Farmington	Connecticut
United States	Houston Methodist Hospital	Houston	Texas
United States	Lancaster Urology	Lancaster	Pennsylvania
United States	Atlantic Urology Medical Group	Long Beach	California
United States	USC Norris Comprehensive Cancer Center	Los Angeles	California
United States	Medical College of Wisconsin - Freodert Hospital	Milwaukee	Wisconsin
United States	Gousse Urology - The Bladder Heath and Reconstructive Urology Institute	Miramar	Florida
United States	Integrity Medical Research	Mountlake Terrace	Washington
United States	Vanderbilt University Medical Center	Nashville	Tennessee
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	Chesapeake Urology Associates, PA	Owings Mills	Maryland
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Advanced Urology Centers of New York	Plainview	New York
United States	UC Davis Medical Center	Sacramento	California
United States	Urological Associates of Southern Arizona, P.C.	Tucson	Arizona
United States	Urology of Virginia, PLLC	Virginia Beach	Virginia
United States	Delaware Valley Urology,IIC	Voorhees	New Jersey
United States	The Iowa Clinic, PC	West Des Moines	Iowa

Sponsors (1)

Lead Sponsor	Collaborator
Ipsen

Countries where clinical trial is conducted

United States,  Canada,  Czechia,  Italy,  Korea, Republic of,  Netherlands,  Poland,  Portugal,  Romania,  Turkey, 

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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
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	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