Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   44155   clinical trials with a EudraCT protocol, of which   7326   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    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

    Summary
    EudraCT number
    		 2015-000507-44
    Trial protocol
    		 DE   BE   ES   FR   LT  
    Global end of trial date
    04 Jul 2019

    Results information
    Results version number
    		 v1(current)
    This version publication date
    15 Jul 2020
    First version publication date
    15 Jul 2020
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    D-FR-52120-223
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02660359
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Ipsen Innovation
    Sponsor organisation address
    5 Avenue du Canada, Les Ulis,, France, 91940
    Public contact
    Medical Director, Ipsen Innovation, clinical.trials@ipsen.com
    Scientific contact
    Medical Director, Ipsen Innovation, clinical.trials@ipsen.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    04 Jul 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    04 Jul 2019
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To assess the efficacy and safety of two doses of Dysport® (600 Units [U] and 800 U) in adult subjects with urinary incontinence (UI) caused by neurogenic detrusor overactivity (NDO) due to spinal cord injury (SCI) or multiple sclerosis (MS) and who had not been adequately managed with oral medication and routinely required clean intermittent catheterisation to manage their bladder function.
    Protection of trial subjects
    The study was conducted under the provisions of the Declaration of Helsinki, and in accordance with the International Conference on Harmonisation Consolidated Guideline on Good Clinical Practice.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    08 Jul 2016
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 16
    Country: Number of subjects enrolled
    United Kingdom: 10
    Country: Number of subjects enrolled
    Belgium: 5
    Country: Number of subjects enrolled
    France: 14
    Country: Number of subjects enrolled
    Germany: 5
    Country: Number of subjects enrolled
    Lithuania: 10
    Country: Number of subjects enrolled
    Argentina: 12
    Country: Number of subjects enrolled
    Australia: 3
    Country: Number of subjects enrolled
    Brazil: 47
    Country: Number of subjects enrolled
    Chile: 5
    Country: Number of subjects enrolled
    Colombia: 22
    Country: Number of subjects enrolled
    Israel: 17
    Country: Number of subjects enrolled
    Mexico: 32
    Country: Number of subjects enrolled
    Peru: 17
    Country: Number of subjects enrolled
    Russian Federation: 38
    Country: Number of subjects enrolled
    Ukraine: 5
    Worldwide total number of subjects
    258
    EEA total number of subjects
    60
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    240
    From 65 to 84 years
    18
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 A total of 258 subjects with UI, caused by NDO due to SCI or MS, were enrolled at 67 study sites worldwide. One of the 258 randomised subjects did not receive any treatment. The study was terminated early by the sponsor due to lack of recruitment.

    Pre-assignment
    Screening details
    		 Subjects were randomised to 1 of 4 sequences: A) placebo in a double-blind placebo-controlled (DBPC) cycle then Dysport® 600 U in subsequent double-blind cycles: B) placebo in DBPC cycle then Dysport® 800 U in subsequent cycles: C) Dysport® 600 U in all cycles: D) Dysport® 800 U in all cycles. The minimum retreatment interval was 12 weeks.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Investigator, Monitor, Carer, Subject

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Subjects were administered placebo on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 millilitres (mL) divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Placebo was injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each.

    Arm title
    		 Dysport® 600 U
    Arm description
    		 Subjects were administered Dysport® 600 U on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Dysport®
    Investigational medicinal product code
    Other name
    AbobotulinumtoxinA
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Dysport® 600 U was injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each.

    Arm title
    		 Dysport® 800 U
    Arm description
    		 Subjects were administered Dysport® 800 U on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Dysport®
    Investigational medicinal product code
    Other name
    AbobotulinumtoxinA
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Dysport® 800 U was injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each.

    Number of subjects in period 1 [1]
    		Placebo Dysport® 600 U Dysport® 800 U
    Started
    86
    86
    85
    Completed
    0
    0
    1
    Not completed
    86
    86
    84
         Consent withdrawn by subject
    7
    5
    8
         Adverse event, non-fatal
    -
    1
    -
         Sponsor Decision to Terminate Study
    73
    75
    71
         Unspecified
    2
    1
    3
         Lost to follow-up
    3
    3
    -
         Lack of efficacy
    1
    1
    1
         Protocol deviation
    -
    -
    1
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: The Baseline Period is based on the 257 subjects that received treatment. One of the 258 randomised subjects did not receive any treatment and is therefore excluded from baseline analyses. This subject is included in the Worldwide Enrolled population but data was not available on the patient's age and so the patient has been included in the larger 18-64 years age group for validation purposes.

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Subjects were administered placebo on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 millilitres (mL) divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.

    Reporting group title
    Dysport® 600 U
    Reporting group description
    		 Subjects were administered Dysport® 600 U on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.

    Reporting group title
    Dysport® 800 U
    Reporting group description
    		 Subjects were administered Dysport® 800 U on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.

    Reporting group values
    		 Placebo Dysport® 600 U Dysport® 800 U Total
    Number of subjects
    		 86 86 85 257
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 80 82 77 239
        From 65-84 years
    		 6 4 8 18
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 42.2 ± 13.16 42.5 ± 12.10 42.0 ± 14.72 -
    Gender categorical
    Units: Subjects
        Female
    		 36 29 30 95
        Male
    		 50 57 55 162
    Race
    Units: Subjects
        American Indian or Alaska Native
    		 8 13 9 30
        Asian
    		 0 0 0 0
        Native Hawaiian or Other Pacific Islander
    		 0 0 1 1
        Black or African American
    		 2 4 4 10
        White
    		 55 52 56 163
        Other
    		 11 6 7 24
        Multiple
    		 7 5 3 15
        Missing
    		 3 6 5 14
    Aetiology of NDO
    Units: Subjects
        SCI
    		 62 64 65 191
        MS
    		 24 22 20 66

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Subjects were administered placebo on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 millilitres (mL) divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.

    Reporting group title
    Dysport® 600 U
    Reporting group description
    		 Subjects were administered Dysport® 600 U on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.

    Reporting group title
    Dysport® 800 U
    Reporting group description
    		 Subjects were administered Dysport® 800 U on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.

    Primary: Mean Change From Baseline in Weekly Number of UI Episodes at Week 6 of DBPC Cycle

    		 Close Top of page
    End point title
    		 Mean Change From Baseline in Weekly Number of UI Episodes at Week 6 of DBPC Cycle
    End point description
    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. Results are presented for the modified intention to treat (mITT) population (all randomised subjects who received at least 1 administration of study treatment). Subjects were analysed as randomised (planned treatment). Only subjects with data available for analysis at Week 6 of DBPC cycle are presented.
    End point type
    Primary
    End point timeframe
    Baseline and Week 6 of DBPC Cycle
    End point values
    		 Placebo Dysport® 600 U Dysport® 800 U
    Number of subjects analysed
    76
    82
    73
    Units: Weekly UI episodes
        least squares mean (standard error)
    -12.86 ± 1.95
    -21.83 ± 1.91
    -22.62 ± 1.88
    Statistical analysis title
    		 Comparison of Dysport® 600 U to Placebo
    Statistical analysis description
    Treatment group, visit (Week 6), treatment-by-visit interaction, recorded stratification factors (aetiology of NDO [SCI or MS], prior intradetrusor [Botulinum toxin [BTX]-naïve or BTX-non-naïve]) and study baseline value (weekly number of UI episodes) as fixed effect variables, and subject as a random effect.
    Comparison groups
    Placebo v Dysport® 600 U
    Number of subjects included in analysis
    158
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    P-value
    		 = 0.0001
    Method
    		 MMRM
    Parameter type
    		 LS Mean Difference
    Point estimate
    -8.97
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13.5
         upper limit
    		 -4.44
    Notes
    [1] - If both p-values for the 2 primary tests (the test of Dysport® 800 U vs. placebo and the test of Dysport® 600 U vs. placebo) were lower than 0.05, both were declared statistically significant. If 1 of the primary tests had a p-value greater than or equal to 0.05, then the other test was declared statistically significant if its p-value was lower than 0.025 and only the significant dose continued in the hierarchal testing strategy.
    Statistical analysis title
    		 Comparison of Dysport® 800 U to Placebo
    Statistical analysis description
    Treatment group, visit (Week 6), treatment-by-visit interaction, recorded stratification factors (aetiology of NDO [SCI or MS], prior intradetrusor [Botulinum toxin [BTX]-naïve or BTX-non-naïve]) and study baseline value (weekly number of UI episodes) as fixed effect variables, and subject as a random effect.
    Comparison groups
    Placebo v Dysport® 800 U
    Number of subjects included in analysis
    149
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [2]
    P-value
    		 < 0.0001
    Method
    		 MMRM
    Parameter type
    		 LS Mean Difference
    Point estimate
    -9.76
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14.41
         upper limit
    		 -5.12
    Notes
    [2] - If both p-values for the 2 primary tests (the test of Dysport® 800 U vs. placebo and the test of Dysport® 600 U vs. placebo) were lower than 0.05, both were declared statistically significant. If 1 of the primary tests had a p-value greater than or equal to 0.05, then the other test was declared statistically significant if its p-value was lower than 0.025 and only the significant dose continued in the hierarchal testing strategy.

    Secondary: Percentage of Subjects With No Episodes of UI at Week 6 of DBPC Cycle

    		 Close Top of page
    End point title
    		 Percentage of Subjects With No Episodes of UI at Week 6 of DBPC Cycle
    End point description
    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. Results are presented for the mITT population (all randomised subjects who received at least 1 administration of study treatment). Subjects were analysed as randomised (planned treatment). Only subjects with data available for analysis at Week 6 of DBPC cycle are presented.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 6 of DBPC Cycle
    End point values
    		 Placebo Dysport® 600 U Dysport® 800 U
    Number of subjects analysed
    76
    82
    73
    Units: Percentage of Subjects
        number (not applicable)
    1.3
    36.6
    26.0
    Statistical analysis title
    		 Comparison of Dysport® 600 U with Placebo
    Statistical analysis description
    Treatment group, recorded stratification factors, visit, treatment-by-visit interaction, study baseline-by-visit interaction and study baseline weekly number of UI episodes as fixed effect.
    Comparison groups
    Placebo v Dysport® 600 U
    Number of subjects included in analysis
    158
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [3]
    P-value
    		 = 0.0002
    Method
    		 Generalised linear mixed model (GLMM)
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    45.55
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 6.09
         upper limit
    		 340.69
    Notes
    [3] - This secondary endpoint was included in the hierarchical analysis and was tested for both doses at the 0.05 level using a hierarchical methodology.
    Statistical analysis title
    		 Comparison of Dysport® 800 U with Placebo
    Statistical analysis description
    Treatment group, recorded stratification factors, visit, treatment-by-visit interaction, study baseline-by-visit interaction and study baseline weekly number of UI episodes as fixed effect.
    Comparison groups
    Placebo v Dysport® 800 U
    Number of subjects included in analysis
    149
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [4]
    P-value
    		 = 0.0009
    Method
    		 GLMM
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    31.69
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.17
         upper limit
    		 240.58
    Notes
    [4] - This secondary endpoint was included in the hierarchical analysis and was tested for both doses at the 0.05 level using a hierarchical methodology.

    Secondary: Percentage of Subjects with a UI Response at Improvement Levels ≥30%, ≥50%, and ≥75% at Week 6 of the DBPC Cycle

    		 Close Top of page
    End point title
    		 Percentage of Subjects with a UI Response at Improvement Levels ≥30%, ≥50%, and ≥75% at Week 6 of the DBPC Cycle
    End point description
    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. Results are presented for the mITT population: all randomised subjects who received at least 1 administration of study treatment. Subjects were analysed as randomised (planned treatment). Only subjects with data available for analysis at Week 6 of DBPC cycle are presented.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 6 of DBPC Cycle
    End point values
    		 Placebo Dysport® 600 U Dysport® 800 U
    Number of subjects analysed
    76
    82
    73
    Units: Percentage of Subjects
    number (not applicable)
        ≥30% Improvement
    55.3
    81.7
    76.7
        ≥50% Improvement
    38.2
    72.0
    61.6
        ≥75% Improvement
    17.1
    62.2
    50.7
    Statistical analysis title
    		 Treatment comparison at ≥30% Improvement
    Statistical analysis description
    Dysport® 600 U versus Placebo. Treatment group, recorded stratification factors, visit, treatment-by-visit interaction, study baseline-by-visit interaction and study baseline weekly number of UI episodes as fixed effect.
    Comparison groups
    Placebo v Dysport® 600 U
    Number of subjects included in analysis
    158
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [5]
    P-value
    		 = 0.0007
    Method
    		 GLMM
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    3.55
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.72
         upper limit
    		 7.34
    Notes
    [5] - This secondary endpoint was not included within the hierarchical testing procedure and was analysed for exploratory purposes only to compare each Dysport® dose to placebo at a 0.05 type one error rate.
    Statistical analysis title
    		 Treatment comparison at ≥30% Improvement
    Statistical analysis description
    Dysport® 800 U versus Placebo. Treatment group, recorded stratification factors, visit, treatment-by-visit interaction, study baseline-by-visit interaction and study baseline weekly number of UI episodes as fixed effect.
    Comparison groups
    Placebo v Dysport® 800 U
    Number of subjects included in analysis
    149
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [6]
    P-value
    		 = 0.0037
    Method
    		 GLMM
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.94
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.43
         upper limit
    		 6.07
    Notes
    [6] - This secondary endpoint was not included within the hierarchical testing procedure and was analysed for exploratory purposes only to compare each Dysport® dose to placebo at a 0.05 type one error rate.
    Statistical analysis title
    		 Treatment comparison at ≥50% Improvement
    Statistical analysis description
    Dysport® 600 U versus Placebo. Treatment group, recorded stratification factors, visit, treatment-by-visit interaction, study baseline-by-visit interaction and study baseline weekly number of UI episodes as fixed effect.
    Comparison groups
    Placebo v Dysport® 600 U
    Number of subjects included in analysis
    158
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [7]
    P-value
    		 < 0.0001
    Method
    		 GLMM
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    3.98
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.03
         upper limit
    		 7.79
    Notes
    [7] - This secondary endpoint was not included within the hierarchical testing procedure and was analysed for exploratory purposes only to compare each Dysport® dose to placebo at a 0.05 type one error rate.
    Statistical analysis title
    		 Treatment comparison at ≥50% Improvement
    Statistical analysis description
    Dysport® 800 U versus Placebo. Treatment group, recorded stratification factors, visit, treatment-by-visit interaction, study baseline-by-visit interaction and study baseline weekly number of UI episodes as fixed effect.
    Comparison groups
    Placebo v Dysport® 800 U
    Number of subjects included in analysis
    149
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [8]
    P-value
    		 = 0.0034
    Method
    		 GLMM
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.73
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.4
         upper limit
    		 5.33
    Notes
    [8] - This secondary endpoint was not included within the hierarchical testing procedure and was analysed for exploratory purposes only to compare each Dysport® dose to placebo at a 0.05 type one error rate.
    Statistical analysis title
    		 Treatment comparison at ≥75% Improvement
    Statistical analysis description
    Dysport® 600 U versus Placebo. Treatment group, recorded stratification factors, visit, treatment-by-visit interaction, study baseline-by-visit interaction and study baseline weekly number of UI episodes as fixed effect.
    Comparison groups
    Placebo v Dysport® 600 U
    Number of subjects included in analysis
    158
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [9]
    P-value
    		 < 0.0001
    Method
    		 GLMM
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    7.38
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.5
         upper limit
    		 15.58
    Notes
    [9] - This secondary endpoint was not included within the hierarchical testing procedure and was analysed for exploratory purposes only to compare each Dysport® dose to placebo at a 0.05 type one error rate.
    Statistical analysis title
    		 Treatment comparison at ≥75% Improvement
    Statistical analysis description
    Dysport® 800 U versus Placebo. Treatment group, recorded stratification factors, visit, treatment-by-visit interaction, study baseline-by-visit interaction and study baseline weekly number of UI episodes as fixed effect.
    Comparison groups
    Placebo v Dysport® 800 U
    Number of subjects included in analysis
    149
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [10]
    P-value
    		 < 0.0001
    Method
    		 GLMM
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    5.28
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.48
         upper limit
    		 11.24
    Notes
    [10] - This secondary endpoint was not included within the hierarchical testing procedure and was analysed for exploratory purposes only to compare each Dysport® dose to placebo at a 0.05 type one error rate.

    Secondary: Median Time Between Treatments

    		 Close Top of page
    End point title
    		 Median Time Between Treatments
    End point description
    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. Results are presented for the mITT population (all randomised subjects who received at least 1 administration of study treatment). Subjects were analysed as randomised (planned treatment).
    End point type
    Secondary
    End point timeframe
    Day of first treatment (baseline) and day of retreatment
    End point values
    		 Placebo Dysport® 600 U Dysport® 800 U
    Number of subjects analysed
    86
    86
    85
    Units: Days
        median (full range (min-max))
    132.0 (8 to 644)
    238.5 (57 to 651)
    210.0 (56 to 649)
    No statistical analyses for this end point

    Secondary: Mean Change From Baseline in Volume Per Void at Week 6 of DBPC Cycle

    		 Close Top of page
    End point title
    		 Mean Change From Baseline in Volume Per Void at Week 6 of DBPC Cycle
    End point description
    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. Results are presented for the mITT population (all randomised subjects who received at least 1 administration of study treatment). Subjects were analysed as randomised (planned treatment). Only subjects with data available for analysis at Week 6 of DBPC cycle are presented.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 6 of DBPC Cycle
    End point values
    		 Placebo Dysport® 600 U Dysport® 800 U
    Number of subjects analysed
    74
    77
    72
    Units: mL
        least squares mean (standard error)
    -6.00 ± 17.80
    90.14 ± 17.45
    84.78 ± 17.22
    Statistical analysis title
    		 Comparison of Dysport® 600 U with Placebo
    Statistical analysis description
    Treatment group, visit (Week 6), treatment-by-visit interaction, recorded stratification factors (aetiology of NDO [SCI or MS], prior intradetrusor [BTX-naïve or BTX-non-naïve]) and study baseline value (total volume per void) as fixed effect variables, and subject as a random effect.
    Comparison groups
    Placebo v Dysport® 600 U
    Number of subjects included in analysis
    151
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [11]
    P-value
    		 < 0.0001
    Method
    		 MMRM
    Parameter type
    		 LS Mean Difference
    Point estimate
    96.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 53.1
         upper limit
    		 139.19
    Notes
    [11] - This secondary endpoint was not included within the hierarchical testing procedure and was analysed for exploratory purposes only to compare each Dysport® dose to placebo at a 0.05 type one error rate.
    Statistical analysis title
    		 Comparison of Dysport® 800 U with Placebo
    Statistical analysis description
    Treatment group, visit (Week 6), treatment-by-visit interaction, recorded stratification factors (aetiology of NDO [SCI or MS], prior intradetrusor [BTX-naïve or BTX-non-naïve]) and study baseline value (total volume per void) as fixed effect variables, and subject as a random effect.
    Comparison groups
    Placebo v Dysport® 800 U
    Number of subjects included in analysis
    146
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [12]
    P-value
    		 < 0.0001
    Method
    		 MMRM
    Parameter type
    		 LS Mean Difference
    Point estimate
    90.78
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 47.07
         upper limit
    		 134.48
    Notes
    [12] - This secondary endpoint was not included within the hierarchical testing procedure and was analysed for exploratory purposes only to compare each Dysport® dose to placebo at a 0.05 type one error rate.

    Secondary: Mean Change From Baseline in Maximum Cystometric Capacity (MCC) at Week 6 of DBPC Cycle

    		 Close Top of page
    End point title
    		 Mean Change From Baseline in Maximum Cystometric Capacity (MCC) at Week 6 of DBPC Cycle
    End point description
    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). Results are presented for the urodynamic population (all subjects in the mITT population included in the urodynamic subset at randomisation). Subjects were analysed as randomised (planned treatment). Only subjects with data available for analysis at Week 6 of DBPC cycle are presented.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 6 of DBPC Cycle
    End point values
    		 Placebo Dysport® 600 U Dysport® 800 U
    Number of subjects analysed
    62
    76
    63
    Units: mL
        least squares mean (standard error)
    3.5 ± 22.83
    178.5 ± 21.38
    171.9 ± 21.58
    Statistical analysis title
    		 Comparison of Dysport® 600 U with Placebo
    Statistical analysis description
    Treatment group, recorded stratification factors (aetiology of NDO [SCI or MS], prior intradetrusor [BTX-naïve or BTX-non-naïve]) and baseline value of MCC as covariates.
    Comparison groups
    Placebo v Dysport® 600 U
    Number of subjects included in analysis
    138
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [13]
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    175
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 122.9
         upper limit
    		 227
    Notes
    [13] - This secondary endpoint was not included within the hierarchical testing procedure and was analysed for exploratory purposes only to compare each Dysport® dose to placebo at a 0.05 type one error rate.
    Statistical analysis title
    		 Comparison of Dysport® 800 U with Placebo
    Statistical analysis description
    Treatment group, recorded stratification factors (aetiology of NDO [SCI or MS], prior intradetrusor [BTX-naïve or BTX-non-naïve]) and baseline value of MCC as covariates.
    Comparison groups
    Placebo v Dysport® 800 U
    Number of subjects included in analysis
    125
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [14]
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    168.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 113.6
         upper limit
    		 223.1
    Notes
    [14] - This secondary endpoint was not included within the hierarchical testing procedure and was analysed for exploratory purposes only to compare each Dysport® dose to placebo at a 0.05 type one error rate.

    Secondary: Mean Change From Baseline in Maximum Detrusor Pressure (MDP) During Storage at Week 6 of DBPC Cycle

    		 Close Top of page
    End point title
    		 Mean Change From Baseline in Maximum Detrusor Pressure (MDP) During Storage at Week 6 of DBPC Cycle
    End point description
    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. Results are presented for the urodynamic population (all subjects in the mITT population included in the urodynamic subset at randomisation). Subjects were analysed as randomised (planned treatment). Only subjects with data available for analysis at Week 6 of DBPC cycle are presented.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 6 of DBPC Cycle
    End point values
    		 Placebo Dysport® 600 U Dysport® 800 U
    Number of subjects analysed
    54
    71
    57
    Units: centimetres of water
        least squares mean (standard error)
    -3.7 ± 3.84
    -36.7 ± 3.48
    -36.2 ± 3.51
    Statistical analysis title
    		 Comparison of Dysport® 600 U with Placebo
    Statistical analysis description
    Treatment group, recorded stratification factors (aetiology of NDO [SCI or MS], prior intradetrusor [BTX-naïve or BTX-non-naïve]) and baseline value of MDP as covariates.
    Comparison groups
    Placebo v Dysport® 600 U
    Number of subjects included in analysis
    125
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [15]
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -32.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -41.5
         upper limit
    		 -24.4
    Notes
    [15] - This secondary endpoint was not included within the hierarchical testing procedure and was analysed for exploratory purposes only to compare each Dysport® dose to placebo at a 0.05 type one error rate.
    Statistical analysis title
    		 Comparison of Dysport® 800 U with Placebo
    Statistical analysis description
    Treatment group, recorded stratification factors (aetiology of NDO [SCI or MS], prior intradetrusor [BTX-naïve or BTX-non-naïve]) and baseline value of MDP as covariates.
    Comparison groups
    Placebo v Dysport® 800 U
    Number of subjects included in analysis
    111
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [16]
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -32.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -41.5
         upper limit
    		 -23.4
    Notes
    [16] - This secondary endpoint was not included within the hierarchical testing procedure and was analysed for exploratory purposes only to compare each Dysport® dose to placebo at a 0.05 type one error rate.

    Secondary: Mean Change From Baseline in Volume at First Involuntary Detrusor Contraction (Vol@1stIDC) at Week 6 of DBPC Cycle

    		 Close Top of page
    End point title
    		 Mean Change From Baseline in Volume at First Involuntary Detrusor Contraction (Vol@1stIDC) at Week 6 of DBPC Cycle
    End point description
    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. Results are presented for the urodynamic population (all subjects in the mITT population included in the urodynamic subset at randomisation). Subjects were analysed as randomised (planned treatment). Only subjects with data available for analysis at Week 6 of DBPC cycle are presented.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 6 of DBPC Cycle
    End point values
    		 Placebo Dysport® 600 U Dysport® 800 U
    Number of subjects analysed
    60
    72
    58
    Units: mL
        least squares mean (standard error)
    15.9 ± 23.34
    168.7 ± 22.09
    185.5 ± 22.80
    Statistical analysis title
    		 Comparison of Dysport® 600 U with Placebo
    Statistical analysis description
    Treatment group, recorded stratification factors (aetiology of NDO [SCI or MS], prior intradetrusor [BTX-naïve or BTX-non-naïve]) and baseline value of Vol@1stIDC as covariates.
    Comparison groups
    Placebo v Dysport® 600 U
    Number of subjects included in analysis
    132
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [17]
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    152.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 99.2
         upper limit
    		 206.5
    Notes
    [17] - This secondary endpoint was not included within the hierarchical testing procedure and was analysed for exploratory purposes only to compare each Dysport® dose to placebo at a 0.05 type one error rate.
    Statistical analysis title
    		 Comparison of Dysport® 800 U with Placebo
    Statistical analysis description
    Treatment group, recorded stratification factors (aetiology of NDO [SCI or MS], prior intradetrusor [BTX-naïve or BTX-non-naïve]) and baseline value of Vol@1stIDC as covariates.
    Comparison groups
    Placebo v Dysport® 800 U
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [18]
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    169.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 111.7
         upper limit
    		 227.6
    Notes
    [18] - This secondary endpoint was not included within the hierarchical testing procedure and was analysed for exploratory purposes only to compare each Dysport® dose to placebo at a 0.05 type one error rate.

    Secondary: Percentage of Subjects With No Involuntary Detrusor Contractions (IDCs) During Storage at Week 6 of DBPC Cycle

    		 Close Top of page
    End point title
    		 Percentage of Subjects With No Involuntary Detrusor Contractions (IDCs) During Storage at Week 6 of DBPC Cycle
    End point description
    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. Results are presented for the urodynamic population (all subjects in the mITT population included in the urodynamic subset at randomisation). Subjects were analysed as randomised (planned treatment). Only subjects with data available for analysis at Week 6 of DBPC cycle are presented.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 6 of DBPC Cycle
    End point values
    		 Placebo Dysport® 600 U Dysport® 800 U
    Number of subjects analysed
    59
    74
    58
    Units: Percentage of Subjects
        number (not applicable)
    3.4
    52.7
    50.0
    Statistical analysis title
    		 Comparison of Dysport® 600 U with Placebo
    Statistical analysis description
    Treatment group, recorded stratification factors, visit, treatment-by-visit interaction, study baseline-by-visit interaction and study baseline weekly number of UI episodes as fixed effect.
    Comparison groups
    Placebo v Dysport® 600 U
    Number of subjects included in analysis
    133
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [19]
    P-value
    		 < 0.0001
    Method
    		 GLMM
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    31.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 7.05
         upper limit
    		 137.09
    Notes
    [19] - This secondary endpoint was not included within the hierarchical testing procedure and was analysed for exploratory purposes only to compare each Dysport® dose to placebo at a 0.05 type one error rate.
    Statistical analysis title
    		 Comparison of Dysport® 800 U with Placebo
    Statistical analysis description
    Treatment group, recorded stratification factors, visit, treatment-by-visit interaction, study baseline-by-visit interaction and study baseline weekly number of UI episodes as fixed effect.
    Comparison groups
    Placebo v Dysport® 800 U
    Number of subjects included in analysis
    117
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [20]
    P-value
    		 < 0.0001
    Method
    		 GLMM
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    28.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 6.24
         upper limit
    		 126.25
    Notes
    [20] - This secondary endpoint was not included within the hierarchical testing procedure and was analysed for exploratory purposes only to compare each Dysport® dose to placebo at a 0.05 type one error rate.

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 32 weeks for both Dysport® groups and approximately 19 weeks for the Placebo group).
    Adverse event reporting additional description
    The safety population included all subjects who received at least 1 administration of study treatment (including only partial administration). Safety subjects were analysed according to their actual treatment received. Number of deaths (all causes) is presented for the duration of the study (up to a maximum of 115 weeks).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Subjects were administered placebo on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.

    Reporting group title
    Dysport® 600 U
    Reporting group description
    		 Subjects were administered Dysport® 600 U on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.

    Reporting group title
    Dysport® 800 U
    Reporting group description
    		 Subjects were administered Dysport® 800 U on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.

    Serious adverse events
    		 Placebo Dysport® 600 U Dysport® 800 U
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 85 (0.00%)
    9 / 87 (10.34%)
    8 / 85 (9.41%)
         number of deaths (all causes)
    0
    1
    0
         number of deaths resulting from adverse events
    0
    1
    0
    Injury, poisoning and procedural complications
    Femur fracture
         subjects affected / exposed
    0 / 85 (0.00%)
    1 / 87 (1.15%)
    0 / 85 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    0 / 85 (0.00%)
    1 / 87 (1.15%)
    1 / 85 (1.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Multiple sclerosis relapse
         subjects affected / exposed
    0 / 85 (0.00%)
    1 / 87 (1.15%)
    1 / 85 (1.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ataxia
         subjects affected / exposed
    0 / 85 (0.00%)
    1 / 87 (1.15%)
    0 / 85 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Multiple sclerosis
         subjects affected / exposed
    0 / 85 (0.00%)
    1 / 87 (1.15%)
    0 / 85 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 85 (0.00%)
    1 / 87 (1.15%)
    1 / 85 (1.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    0 / 85 (0.00%)
    1 / 87 (1.15%)
    0 / 85 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gait disturbance
         subjects affected / exposed
    0 / 85 (0.00%)
    0 / 87 (0.00%)
    1 / 85 (1.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 85 (0.00%)
    1 / 87 (1.15%)
    0 / 85 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    0 / 85 (0.00%)
    1 / 87 (1.15%)
    0 / 85 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    0 / 85 (0.00%)
    1 / 87 (1.15%)
    1 / 85 (1.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 85 (0.00%)
    0 / 87 (0.00%)
    1 / 85 (1.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    0 / 85 (0.00%)
    1 / 87 (1.15%)
    0 / 85 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteomyelitis chronic
         subjects affected / exposed
    0 / 85 (0.00%)
    1 / 87 (1.15%)
    0 / 85 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Perineal abscess
         subjects affected / exposed
    0 / 85 (0.00%)
    1 / 87 (1.15%)
    0 / 85 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Soft tissue infection
         subjects affected / exposed
    0 / 85 (0.00%)
    1 / 87 (1.15%)
    0 / 85 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Testicular abscess
         subjects affected / exposed
    0 / 85 (0.00%)
    1 / 87 (1.15%)
    0 / 85 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 85 (0.00%)
    0 / 87 (0.00%)
    1 / 85 (1.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Orchitis
         subjects affected / exposed
    0 / 85 (0.00%)
    0 / 87 (0.00%)
    1 / 85 (1.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyperglycaemia
         subjects affected / exposed
    0 / 85 (0.00%)
    1 / 87 (1.15%)
    0 / 85 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 2%
    Non-serious adverse events
    		 Placebo Dysport® 600 U Dysport® 800 U
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    34 / 85 (40.00%)
    40 / 87 (45.98%)
    42 / 85 (49.41%)
    Investigations
    Nitrite urine present
         subjects affected / exposed
    2 / 85 (2.35%)
    2 / 87 (2.30%)
    0 / 85 (0.00%)
         occurrences all number
    2
    2
    0
    Blood urine present
         subjects affected / exposed
    2 / 85 (2.35%)
    0 / 87 (0.00%)
    0 / 85 (0.00%)
         occurrences all number
    2
    0
    0
    Injury, poisoning and procedural complications
    Anaesthetic complication cardiac
         subjects affected / exposed
    0 / 85 (0.00%)
    2 / 87 (2.30%)
    1 / 85 (1.18%)
         occurrences all number
    0
    2
    1
    Vascular disorders
    Haemorrhage
         subjects affected / exposed
    0 / 85 (0.00%)
    2 / 87 (2.30%)
    1 / 85 (1.18%)
         occurrences all number
    0
    2
    1
    Hypotension
         subjects affected / exposed
    2 / 85 (2.35%)
    2 / 87 (2.30%)
    1 / 85 (1.18%)
         occurrences all number
    2
    2
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    0 / 85 (0.00%)
    1 / 87 (1.15%)
    3 / 85 (3.53%)
         occurrences all number
    0
    1
    5
    Muscle spasticity
         subjects affected / exposed
    0 / 85 (0.00%)
    2 / 87 (2.30%)
    1 / 85 (1.18%)
         occurrences all number
    0
    2
    1
    Neuralgia
         subjects affected / exposed
    0 / 85 (0.00%)
    2 / 87 (2.30%)
    0 / 85 (0.00%)
         occurrences all number
    0
    2
    0
    Dizziness
         subjects affected / exposed
    2 / 85 (2.35%)
    0 / 87 (0.00%)
    0 / 85 (0.00%)
         occurrences all number
    2
    0
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 85 (0.00%)
    2 / 87 (2.30%)
    1 / 85 (1.18%)
         occurrences all number
    0
    2
    1
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    1 / 85 (1.18%)
    3 / 87 (3.45%)
    2 / 85 (2.35%)
         occurrences all number
    1
    5
    2
    Fatigue
         subjects affected / exposed
    0 / 85 (0.00%)
    1 / 87 (1.15%)
    2 / 85 (2.35%)
         occurrences all number
    0
    1
    2
    Malaise
         subjects affected / exposed
    1 / 85 (1.18%)
    2 / 87 (2.30%)
    0 / 85 (0.00%)
         occurrences all number
    1
    2
    0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    3 / 85 (3.53%)
    3 / 87 (3.45%)
    4 / 85 (4.71%)
         occurrences all number
    3
    7
    4
    Constipation
         subjects affected / exposed
    1 / 85 (1.18%)
    4 / 87 (4.60%)
    2 / 85 (2.35%)
         occurrences all number
    1
    4
    2
    Abdominal pain
         subjects affected / exposed
    2 / 85 (2.35%)
    1 / 87 (1.15%)
    2 / 85 (2.35%)
         occurrences all number
    2
    2
    2
    Abdominal pain lower
         subjects affected / exposed
    2 / 85 (2.35%)
    0 / 87 (0.00%)
    2 / 85 (2.35%)
         occurrences all number
    2
    0
    2
    Nausea
         subjects affected / exposed
    0 / 85 (0.00%)
    2 / 87 (2.30%)
    0 / 85 (0.00%)
         occurrences all number
    0
    2
    0
    Reproductive system and breast disorders
    Erectile dysfunction
         subjects affected / exposed
    0 / 85 (0.00%)
    0 / 87 (0.00%)
    2 / 85 (2.35%)
         occurrences all number
    0
    0
    2
    Psychiatric disorders
    Depression
         subjects affected / exposed
    0 / 85 (0.00%)
    0 / 87 (0.00%)
    2 / 85 (2.35%)
         occurrences all number
    0
    0
    2
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    4 / 85 (4.71%)
    5 / 87 (5.75%)
    4 / 85 (4.71%)
         occurrences all number
    4
    5
    4
    Leukocyturia
         subjects affected / exposed
    0 / 85 (0.00%)
    1 / 87 (1.15%)
    2 / 85 (2.35%)
         occurrences all number
    0
    1
    3
    Bladder pain
         subjects affected / exposed
    2 / 85 (2.35%)
    1 / 87 (1.15%)
    0 / 85 (0.00%)
         occurrences all number
    2
    1
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    2 / 85 (2.35%)
    3 / 87 (3.45%)
    5 / 85 (5.88%)
         occurrences all number
    2
    5
    6
    Arthralgia
         subjects affected / exposed
    0 / 85 (0.00%)
    2 / 87 (2.30%)
    1 / 85 (1.18%)
         occurrences all number
    0
    3
    1
    Myalgia
         subjects affected / exposed
    0 / 85 (0.00%)
    0 / 87 (0.00%)
    2 / 85 (2.35%)
         occurrences all number
    0
    0
    2
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    17 / 85 (20.00%)
    19 / 87 (21.84%)
    22 / 85 (25.88%)
         occurrences all number
    21
    24
    34
    Bacteriuria
         subjects affected / exposed
    0 / 85 (0.00%)
    6 / 87 (6.90%)
    1 / 85 (1.18%)
         occurrences all number
    0
    6
    1
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 85 (1.18%)
    0 / 87 (0.00%)
    4 / 85 (4.71%)
         occurrences all number
    1
    0
    4
    Influenza
         subjects affected / exposed
    5 / 85 (5.88%)
    2 / 87 (2.30%)
    1 / 85 (1.18%)
         occurrences all number
    5
    2
    1
    Nasopharyngitis
         subjects affected / exposed
    0 / 85 (0.00%)
    1 / 87 (1.15%)
    2 / 85 (2.35%)
         occurrences all number
    0
    1
    2
    Pharyngitis
         subjects affected / exposed
    2 / 85 (2.35%)
    1 / 87 (1.15%)
    1 / 85 (1.18%)
         occurrences all number
    2
    1
    1

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    20 Apr 2018
    Amendment included the following changes: • Decrease in sample size from 408 to 330 subjects; statistical power lowered from 90% to 80%. • Clarification added regarding the primary analysis (i.e. previously referred to as an 'interim' analysis). • Removal of the internal data monitoring committee. • Clarification added throughout the protocol regarding description of the Screening period (i.e. time between Screening Visit 1 and Screening Visit 2, as well as time between Screening and administration of study treatment).

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    This study was terminated early by the sponsor on 04 October 2018, due to slow subject recruitment (258 subjects randomised compared to 330 planned subjects). Only primary and key secondary efficacy analyses were performed.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA