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

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Conditions: Urinary Incontinence; Overactive Bladder
• Interventions: Biological: Botulinum toxin type A; Drug: Placebo
• Enrollment: 258

Participant Flow

Recruitment Details	A total of 258 subjects with urinary incontinence (UI) caused by neurogenic detrusor overactivity (NDO) due to spinal cord injury (SCI) or multiple sclerosis (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 Details	Subjects were randomised to 1 of 4 sequences: A) placebo in a double-blind placebo-controlled (DBPC) cycle then Dysport® 600 Units (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.

Arm/Group Title	Placebo	Dysport® 600 U	Dysport® 800 U
Arm/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.	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.	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.
Period Title: Overall Study
Started [1]	86	86	85
Subjects Entered in the Dysport Cycles	56	86	85
Completed [2]	0	0	1
Not Completed	86	86	84
Reason Not Completed
Protocol Deviation	0	0	1
Sponsor Decision to Terminate Study	73	75	71
Lack of Efficacy	1	1	1
Adverse Event	0	1	0
Other	2	1	3
Withdrawal by Subject	7	5	8
Lost to Follow-up	3	3	0
[1] Subjects randomised and treated in DBPC cycle; [2] Subjects completed the study in the Dysport cycles

Baseline Characteristics

Arm/Group Title		Placebo	Dysport® 600 U	Dysport® 800 U	Total
Arm/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.	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.	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.	Total of all reporting groups
Overall Number of Baseline Participants		86	86	85	257
Baseline Analysis Population Description		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).
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	86 participants	86 participants	85 participants	257 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	80 93.0%	82 95.3%	77 90.6%	239 93.0%
	>=65 years	6 7.0%	4 4.7%	8 9.4%	18 7.0%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	86 participants	86 participants	85 participants	257 participants
		42.2 (13.16)	42.5 (12.10)	42.0 (14.72)	42.2 (13.31)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	86 participants	86 participants	85 participants	257 participants
	Female	36 41.9%	29 33.7%	30 35.3%	95 37.0%
	Male	50 58.1%	57 66.3%	55 64.7%	162 63.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	86 participants	86 participants	85 participants	257 participants
	American Indian or Alaska Native	8 9.3%	13 15.1%	9 10.6%	30 11.7%
	Asian	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	1 1.2%	1 0.4%
	Black or African American	2 2.3%	4 4.7%	4 4.7%	10 3.9%
	White	55 64.0%	52 60.5%	56 65.9%	163 63.4%
	More than one race	7 8.1%	5 5.8%	3 3.5%	15 5.8%
	Unknown or Not Reported	14 16.3%	12 14.0%	12 14.1%	38 14.8%
Aetiology of NDO; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	86 participants	86 participants	85 participants	257 participants
	SCI	62 72.1%	64 74.4%	65 76.5%	191 74.3%
	MS	24 27.9%	22 25.6%	20 23.5%	66 25.7%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	Dysport® 600 U	Dysport® 800 U
Arm/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.	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.	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.
Overall Number of Participants Analyzed	76	82	73
Least Squares Mean (Standard Error); Unit of Measure: Weekly UI episodes
	-12.86 (1.95)	-21.83 (1.91)	-22.62 (1.88)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dysport® 600 U
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	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 Test of Hypothesis	P-Value	0.0001
	Comments	[Not Specified]
	Method	MMLM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-8.97
	Confidence Interval	(2-Sided) 95%; -13.5 to -4.44
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dysport® 800 U
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	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 Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	MMLM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-9.76
	Confidence Interval	(2-Sided) 95%; -14.41 to -5.12
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Percentage of Subjects With No Episodes of UI at Week 6 of DBPC Cycle
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.
Time Frame	Baseline and Week 6 of DBPC Cycle

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	Dysport® 600 U	Dysport® 800 U
Arm/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.	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.	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.
Overall Number of Participants Analyzed	76	82	73
Measure Type: Number; Unit of Measure: Percentage of Subjects
	1.3	36.6	26.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dysport® 600 U
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	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 Test of Hypothesis	P-Value	0.0002
	Comments	[Not Specified]
	Method	Generalised linear mixed model (GLMM)
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	45.55
	Confidence Interval	(2-Sided) 95%; 6.09 to 340.69
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dysport® 800 U
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	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 Test of Hypothesis	P-Value	0.0009
	Comments	[Not Specified]
	Method	GLMM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	31.69
	Confidence Interval	(2-Sided) 95%; 4.17 to 240.58
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Percentage of Subjects With a UI Response at Improvement Levels ≥30%, ≥50%, and ≥75% at Week 6 of the DBPC Cycle
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.
Time Frame	Baseline and Week 6 of DBPC Cycle

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	Dysport® 600 U	Dysport® 800 U
Arm/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.	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.	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.
Overall Number of Participants Analyzed	76	82	73
Measure Type: Number; Unit of Measure: Percentage of Subjects
≥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 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dysport® 600 U
	Comments	Treatment comparison at ≥30% Improvement Level: Dysport® 600 U versus Placebo.
	Type of Statistical Test	Superiority
	Comments	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.
Statistical Test of Hypothesis	P-Value	0.0007
	Comments	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.
	Method	GLMM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.55
	Confidence Interval	(2-Sided) 95%; 1.72 to 7.34
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dysport® 800 U
	Comments	Treatment comparison at ≥30% Improvement Level: Dysport® 800 U versus Placebo
	Type of Statistical Test	Superiority
	Comments	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.
Statistical Test of Hypothesis	P-Value	0.0037
	Comments	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.
	Method	GLMM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.94
	Confidence Interval	(2-Sided) 95%; 1.43 to 6.07
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dysport® 600 U
	Comments	Treatment comparison at ≥50% Improvement level: Dysport® 600 U versus Placebo
	Type of Statistical Test	Superiority
	Comments	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.
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	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.
	Method	GLMM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.98
	Confidence Interval	(2-Sided) 95%; 2.03 to 7.79
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dysport® 800 U
	Comments	Treatment comparison at ≥50% Improvement level: Dysport® 800 U versus Placebo
	Type of Statistical Test	Superiority
	Comments	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.
Statistical Test of Hypothesis	P-Value	0.0034
	Comments	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.
	Method	GLMM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.73
	Confidence Interval	(2-Sided) 95%; 1.40 to 5.33
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dysport® 600 U
	Comments	Treatment comparison at ≥75% Improvement level: Dysport® 600 U versus Placebo
	Type of Statistical Test	Superiority
	Comments	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.
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	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.
	Method	GLMM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	7.38
	Confidence Interval	(2-Sided) 95%; 3.5 to 15.58
	Estimation Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dysport® 800 U
	Comments	Treatment comparison at ≥75% Improvement level: Dysport® 800 U versus Placebo
	Type of Statistical Test	Superiority
	Comments	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.
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	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.
	Method	GLMM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	5.28
	Confidence Interval	(2-Sided) 95%; 2.48 to 11.24
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Median Time Between Treatments
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.
Time Frame	Day of first treatment (baseline) to day of retreatment, up to 2 years

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Placebo	Dysport® 600 U	Dysport® 800 U
Arm/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.	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.	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.
Overall Number of Participants Analyzed	86	86	85
Median (Full Range); Unit of Measure: Days
	132.0; (8.0 to 644.0)	238.5; (57.0 to 651.0)	210.0; (56.0 to 649.0)

5. Secondary Outcome

Title	Mean Change From Baseline in Volume Per Void at Week 6 of DBPC Cycle
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.
Time Frame	Baseline and Week 6 of DBPC Cycle

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	Dysport® 600 U	Dysport® 800 U
Arm/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.	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.	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.
Overall Number of Participants Analyzed	74	77	72
Least Squares Mean (Standard Error); Unit of Measure: mL
	-6.00 (17.80)	90.14 (17.45)	84.78 (17.22)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dysport® 600 U
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	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 Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	96.14
	Confidence Interval	(2-Sided) 95%; 53.10 to 139.19
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dysport® 800 U
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	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 Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	90.78
	Confidence Interval	(2-Sided) 95%; 47.07 to 134.48
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	Mean Change From Baseline in Maximum Cystometric Capacity (MCC) at Week 6 of DBPC Cycle
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).
Time Frame	Baseline and Week 6 of DBPC Cycle

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	Dysport® 600 U	Dysport® 800 U
Arm/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.	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.	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.
Overall Number of Participants Analyzed	62	76	63
Least Squares Mean (Standard Error); Unit of Measure: mL
	3.5 (22.83)	178.5 (21.38)	171.9 (21.58)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dysport® 600 U
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	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 Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	175.0
	Confidence Interval	(2-Sided) 95%; 122.90 to 227.0
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dysport® 800 U
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	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 Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	168.4
	Confidence Interval	(2-Sided) 95%; 113.6 to 223.1
	Estimation Comments	[Not Specified]

7. Secondary Outcome

Title	Mean Change From Baseline in Maximum Detrusor Pressure (MDP) During Storage at Week 6 of DBPC Cycle
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.
Time Frame	Baseline and Week 6 of DBPC Cycle

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	Dysport® 600 U	Dysport® 800 U
Arm/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.	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.	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.
Overall Number of Participants Analyzed	54	71	57
Least Squares Mean (Standard Error); Unit of Measure: centimetres of water
	-3.7 (3.84)	-36.7 (3.48)	-36.2 (3.51)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dysport® 600 U
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	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 Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-32.9
	Confidence Interval	(2-Sided) 95%; -41.5 to -24.4
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dysport® 800 U
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	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 Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-32.5
	Confidence Interval	(2-Sided) 95%; -41.5 to -23.4
	Estimation Comments	[Not Specified]

8. Secondary Outcome

Title	Mean Change From Baseline in Volume at First Involuntary Detrusor Contraction (Vol@1stIDC) at Week 6 of DBPC Cycle
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.
Time Frame	Baseline and Week 6 of DBPC Cycle

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	Dysport® 600 U	Dysport® 800 U
Arm/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.	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.	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.
Overall Number of Participants Analyzed	60	72	58
Least Squares Mean (Standard Error); Unit of Measure: mL
	15.9 (23.34)	168.7 (22.09)	185.5 (22.80)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dysport® 600 U
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	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 Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	152.8
	Confidence Interval	(2-Sided) 95%; 99.2 to 206.5
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dysport® 800 U
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	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 Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	169.7
	Confidence Interval	(2-Sided) 95%; 111.7 to 227.6
	Estimation Comments	[Not Specified]

9. Secondary Outcome

Title	Percentage of Subjects With No Involuntary Detrusor Contraction (IDCs) During Storage at Week 6 of DBPC Cycle
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.
Time Frame	Baseline and Week 6 of DBPC Cycle

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	Dysport® 600 U	Dysport® 800 U
Arm/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.	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.	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.
Overall Number of Participants Analyzed	59	74	58
Measure Type: Number; Unit of Measure: Percentage of Subjects
	3.4	52.7	50.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dysport® 800 U
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	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 Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	GLMM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	31.1
	Confidence Interval	(2-Sided) 95%; 7.05 to 137.09
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dysport® 800 U
	Comments	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.
	Type of Statistical Test	Superiority
	Comments	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 Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	GLMM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	28.08
	Confidence Interval	(2-Sided) 95%; 6.24 to 126.25
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	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 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. One subject randomised to placebo received Dysport 600 U, and 1 subject randomised to Dysport 800 U did not receive treatment and was not included in the safety population. Number of deaths (all causes) is presented for the duration of the study (up to a maximum of 115 weeks).
Arm/Group Title	Placebo		Dysport® 600 U		Dysport® 800 U
Arm/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.		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.		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.
All-Cause Mortality
	Placebo		Dysport® 600 U		Dysport® 800 U
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/85 (0.00%)		1/87 (1.15%)		0/85 (0.00%)
Serious Adverse Events
	Placebo		Dysport® 600 U		Dysport® 800 U
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/85 (0.00%)		9/87 (10.34%)		8/85 (9.41%)
Blood and lymphatic system disorders
Anaemia † 1	0/85 (0.00%)	0	1/87 (1.15%)	1	1/85 (1.18%)	1
General disorders
Chest pain † 1	0/85 (0.00%)	0	1/87 (1.15%)	2	0/85 (0.00%)	0
Gait disturbance † 1	0/85 (0.00%)	0	0/87 (0.00%)	0	1/85 (1.18%)	1
Infections and infestations
Urinary tract infection † 1	0/85 (0.00%)	0	1/87 (1.15%)	1	1/85 (1.18%)	1
Diverticulitis † 1	0/85 (0.00%)	0	0/87 (0.00%)	0	1/85 (1.18%)	1
Osteomyelitis † 1	0/85 (0.00%)	0	1/87 (1.15%)	1	0/85 (0.00%)	0
Osteomyelitis chronic † 1	0/85 (0.00%)	0	1/87 (1.15%)	1	0/85 (0.00%)	0
Perineal abscess † 1	0/85 (0.00%)	0	1/87 (1.15%)	1	0/85 (0.00%)	0
Soft tissue infection † 1	0/85 (0.00%)	0	1/87 (1.15%)	1	0/85 (0.00%)	0
Testicular abscess † 1	0/85 (0.00%)	0	1/87 (1.15%)	1	0/85 (0.00%)	0
Urosepsis † 1	0/85 (0.00%)	0	0/87 (0.00%)	0	1/85 (1.18%)	1
Orchitis † 1	0/85 (0.00%)	0	0/87 (0.00%)	0	1/85 (1.18%)	1
Injury, poisoning and procedural complications
Femur fracture † 1	0/85 (0.00%)	0	1/87 (1.15%)	1	0/85 (0.00%)	0
Metabolism and nutrition disorders
Hyperglycaemia † 1	0/85 (0.00%)	0	1/87 (1.15%)	2	0/85 (0.00%)	0
Nervous system disorders
Cerebrovascular accident † 1	0/85 (0.00%)	0	1/87 (1.15%)	1	1/85 (1.18%)	1
Multiple sclerosis relapse † 1	0/85 (0.00%)	0	1/87 (1.15%)	1	1/85 (1.18%)	1
Ataxia † 1	0/85 (0.00%)	0	1/87 (1.15%)	1	0/85 (0.00%)	0
Multiple sclerosis † 1	0/85 (0.00%)	0	1/87 (1.15%)	2	0/85 (0.00%)	0
Renal and urinary disorders
Haematuria † 1	0/85 (0.00%)	0	1/87 (1.15%)	1	0/85 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea † 1	0/85 (0.00%)	0	1/87 (1.15%)	2	0/85 (0.00%)	0
1 Term from vocabulary, MedDRA 22.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	2%
	Placebo		Dysport® 600 U		Dysport® 800 U
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	34/85 (40.00%)		40/87 (45.98%)		42/85 (49.41%)
Blood and lymphatic system disorders
Anaemia † 1	0/85 (0.00%)	0	2/87 (2.30%)	2	1/85 (1.18%)	1
Gastrointestinal disorders
Diarrhoea † 1	3/85 (3.53%)	3	3/87 (3.45%)	7	4/85 (4.71%)	4
Constipation † 1	1/85 (1.18%)	1	4/87 (4.60%)	4	2/85 (2.35%)	2
Abdominal pain † 1	2/85 (2.35%)	2	1/87 (1.15%)	2	2/85 (2.35%)	2
Abdominal pain lower † 1	2/85 (2.35%)	2	0/87 (0.00%)	0	2/85 (2.35%)	2
Nausea † 1	0/85 (0.00%)	0	2/87 (2.30%)	2	0/85 (0.00%)	0
General disorders
Pyrexia † 1	1/85 (1.18%)	1	3/87 (3.45%)	5	2/85 (2.35%)	2
Fatigue † 1	0/85 (0.00%)	0	1/87 (1.15%)	1	2/85 (2.35%)	2
Malaise † 1	1/85 (1.18%)	1	2/87 (2.30%)	2	0/85 (0.00%)	0
Infections and infestations
Urinary tract infection † 1	17/85 (20.00%)	21	19/87 (21.84%)	24	22/85 (25.88%)	34
Bacteriuria † 1	0/85 (0.00%)	0	6/87 (6.90%)	6	1/85 (1.18%)	1
Upper respiratory tract infection † 1	1/85 (1.18%)	1	0/87 (0.00%)	0	4/85 (4.71%)	4
Influenza † 1	5/85 (5.88%)	5	2/87 (2.30%)	2	1/85 (1.18%)	1
Nasopharyngitis † 1	0/85 (0.00%)	0	1/87 (1.15%)	1	2/85 (2.35%)	2
Pharyngitis † 1	2/85 (2.35%)	2	1/87 (1.15%)	1	1/85 (1.18%)	1
Injury, poisoning and procedural complications
Anaesthetic complication cardiac † 1	0/85 (0.00%)	0	2/87 (2.30%)	2	1/85 (1.18%)	1
Investigations
Nitrite urine present † 1	2/85 (2.35%)	2	2/87 (2.30%)	2	0/85 (0.00%)	0
Blood urine present † 1	2/85 (2.35%)	2	0/87 (0.00%)	0	0/85 (0.00%)	0
Musculoskeletal and connective tissue disorders
Back pain † 1	2/85 (2.35%)	2	3/87 (3.45%)	5	5/85 (5.88%)	6
Arthralgia † 1	0/85 (0.00%)	0	2/87 (2.30%)	3	1/85 (1.18%)	1
Myalgia † 1	0/85 (0.00%)	0	0/87 (0.00%)	0	2/85 (2.35%)	2
Nervous system disorders
Headache † 1	0/85 (0.00%)	0	1/87 (1.15%)	1	3/85 (3.53%)	5
Muscle spasticity † 1	0/85 (0.00%)	0	2/87 (2.30%)	2	1/85 (1.18%)	1
Neuralgia † 1	0/85 (0.00%)	0	2/87 (2.30%)	2	0/85 (0.00%)	0
Dizziness † 1	2/85 (2.35%)	2	0/87 (0.00%)	0	0/85 (0.00%)	0
Psychiatric disorders
Depression † 1	0/85 (0.00%)	0	0/87 (0.00%)	0	2/85 (2.35%)	2
Renal and urinary disorders
Haematuria † 1	4/85 (4.71%)	4	5/87 (5.75%)	5	4/85 (4.71%)	4
Leukocyturia † 1	0/85 (0.00%)	0	1/87 (1.15%)	1	2/85 (2.35%)	3
Bladder pain † 1	2/85 (2.35%)	2	1/87 (1.15%)	1	0/85 (0.00%)	0
Reproductive system and breast disorders
Erectile dysfunction † 1	0/85 (0.00%)	0	0/87 (0.00%)	0	2/85 (2.35%)	2
Vascular disorders
Haemorrhage † 1	0/85 (0.00%)	0	2/87 (2.30%)	2	1/85 (1.18%)	1
Hypotension † 1	2/85 (2.35%)	2	2/87 (2.30%)	2	1/85 (1.18%)	1
1 Term from vocabulary, MedDRA 22.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

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.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Medical Director
• Organization: Ipsen
• Phone: See email
• EMail: clinical.trials@ipsen.com

• Responsible Party: Ipsen
• ClinicalTrials.gov Identifier: NCT02660359
• Other Study ID Numbers: D-FR-52120-223; 2015-000507-44 ( EudraCT Number )
• First Submitted: January 14, 2016
• First Posted: January 21, 2016
• Results First Submitted: May 21, 2021
• Results First Posted: June 16, 2021
• Last Update Posted: September 28, 2022