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

• ClinicalTrials.gov Identifier: NCT02660359
• Recruitment Status: Terminated
• First Posted: January 21, 2016
• Results First Posted: June 16, 2021
• Last Update Posted: September 28, 2022
• Sponsor: Ipsen
• Information provided by (Responsible Party): Ipsen

Tracking Information

• First Submitted Date: January 14, 2016
• First Posted Date: January 21, 2016
• Results First Submitted Date: May 21, 2021
• Results First Posted Date: June 16, 2021
• Last Update Posted Date: September 28, 2022
• Actual Study Start Date: July 8, 2016
• Actual Primary Completion Date: November 9, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 21, 2021)

Mean Change From Baseline in Weekly Number of UI Episodes at Week 6 of DBPC Cycle [ Time Frame: Baseline 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.

Original Primary Outcome Measures (submitted: January 18, 2016)

Change in weekly number of UI episodes [ Time Frame: Baseline, 6 weeks ]

measured on a 7-day bladder diary

Current Secondary Outcome Measures (submitted: July 1, 2021)

• Percentage of Subjects With No Episodes of UI at Week 6 of DBPC Cycle [ Time Frame: Baseline 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 Cycle [ Time Frame: Baseline 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.
• Median Time Between Treatments [ Time Frame: Day 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 Volume Per Void at Week 6 of DBPC Cycle [ Time Frame: Baseline 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 Maximum Cystometric Capacity (MCC) at Week 6 of DBPC Cycle [ Time Frame: Baseline 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).
• Mean Change From Baseline in Maximum Detrusor Pressure (MDP) During Storage at Week 6 of DBPC Cycle [ Time Frame: Baseline 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.
• Mean Change From Baseline in Volume at First Involuntary Detrusor Contraction (Vol@1stIDC) at Week 6 of DBPC Cycle [ Time Frame: Baseline 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.
• Percentage of Subjects With No Involuntary Detrusor Contraction (IDCs) During Storage at Week 6 of DBPC Cycle [ Time Frame: Baseline 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.

Original Secondary Outcome Measures (submitted: January 18, 2016)

• Proportion of subjects with no episodes of UI [ Time Frame: Baseline, 6 weeks ]
  measured on a 7-day bladder diary
• Change in incontinence quality of life (I-QoL) total summary score [ Time Frame: Baseline, 6 weeks ]
  Patient-reported outcome questionnaire

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Dysport® Treatment of Urinary Incontinence in Adults Subjects With Neurogenic Detrusor Overactivity (NDO) Due to Spinal Cord Injury or Multiple Sclerosis - Study 2
• 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment

Condition

• Urinary Incontinence
• Overactive Bladder

Intervention

• 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
• 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

Study Arms

• Experimental: 600 U Dysport® Group
  Intervention: Biological: Botulinum toxin type A
• Placebo Comparator: 600 U Dysport® Placebo Group
  Intervention: Drug: Placebo
• Experimental: 800 U Dysport® Group
  Intervention: Biological: Botulinum toxin type A
• Placebo Comparator: 800 U Dysport® Placebo Group
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: November 29, 2018): 258
• Original Estimated Enrollment (submitted: January 18, 2016): 408
• Actual Study Completion Date: July 4, 2019
• Actual Primary Completion Date: November 9, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Belgium, Brazil, Chile, Colombia, France, Germany, Israel, Lithuania, Mexico, Peru, Russian Federation, Spain, Ukraine, United Kingdom
• Removed Location Countries: New Zealand

Administrative Information

• NCT Number: NCT02660359
• Other Study ID Numbers: D-FR-52120-223; 2015-000507-44 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

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.

• 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.
• Access Criteria: Further details on Ipsen's sharing criteria, eligible studies and process for sharing are available here (https://vivli.org/members/ourmembers/).
• URL: https://vivli.org/members/ourmembers/

• Current Responsible Party: Ipsen
• Original Responsible Party: Same as current
• Current Study Sponsor: Ipsen
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Ipsen Medical Director; Ipsen

• PRS Account: Ipsen
• Verification Date: September 2022