Trial Outcomes & Findings for Dysport® Treatment of Urinary Incontinence in Adults Subjects With Neurogenic Detrusor Overactivity (NDO) Due to Spinal Cord Injury or Multiple Sclerosis - Study 1 (NCT NCT02660138)

NCT ID: NCT02660138

Last Updated: 2022-09-28

Results Overview

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.

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 227 participants
• Primary outcome timeframe: Baseline and Week 6 of DBPC Cycle
• Results posted on: 2022-09-28

Participant Flow

A total of 227 subjects with urinary incontinence (UI) caused by neurogenic detrusor overactivity (NDO) due to spinal cord injury (SCI) or multiple sclerosis (MS) were randomised at 64 study sites worldwide. One randomised subject was not eligible for entry and did not receive treatment. Hence, 226 subjects were randomised and treated during the study. The study was terminated early by the sponsor due to lack of recruitment.

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 re-treatment interval was 12 weeks.

Participant milestones

Measure	Placebo 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.	Dysport® 600 U 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.	Dysport® 800 U 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 Study STARTED	76	76	75
Overall Study Subjects Treated in DBPC Cycle	76	75	75
Overall Study Subjects Entered in the Dysport Cycles	49	75	75
Overall Study COMPLETED	6	2	3
Overall Study NOT COMPLETED	70	74	72

Reasons for withdrawal

Measure	Placebo 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.	Dysport® 600 U 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.	Dysport® 800 U 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 Study Adverse Event	0	3	2
Overall Study Lack of Efficacy	1	2	1
Overall Study Withdrawal by Subject	7	6	6
Overall Study Lost to Follow-up	4	4	1
Overall Study Sponsor Decision to Terminate Study	57	57	62
Overall Study Other	1	1	0
Overall Study Not treated	0	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Placebo n=76 Participants 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.	Dysport® 600 U n=75 Participants Subjects were administered Dysport® 600 U for the first study treatment administration 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.	Dysport® 800 U n=75 Participants Subjects were administered Dysport® 800 U for the first study treatment administration 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 n=226 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	68 Participants n=5 Participants	71 Participants n=7 Participants	66 Participants n=5 Participants	205 Participants n=4 Participants
Age, Categorical >=65 years	8 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants	21 Participants n=4 Participants
Age, Continuous	45.9 years STANDARD_DEVIATION 13.15 • n=5 Participants	43.0 years STANDARD_DEVIATION 12.38 • n=7 Participants	46.8 years STANDARD_DEVIATION 13.58 • n=5 Participants	45.3 years STANDARD_DEVIATION 13.09 • n=4 Participants
Sex: Female, Male Female	38 Participants n=5 Participants	27 Participants n=7 Participants	30 Participants n=5 Participants	95 Participants n=4 Participants
Sex: Female, Male Male	38 Participants n=5 Participants	48 Participants n=7 Participants	45 Participants n=5 Participants	131 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	10 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	11 Participants n=4 Participants
Race (NIH/OMB) White	65 Participants n=5 Participants	70 Participants n=7 Participants	64 Participants n=5 Participants	199 Participants n=4 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	5 Participants n=4 Participants
Aetiology of NDO SCI	51 Participants n=5 Participants	49 Participants n=7 Participants	48 Participants n=5 Participants	148 Participants n=4 Participants
Aetiology of NDO MS	25 Participants n=5 Participants	26 Participants n=7 Participants	27 Participants n=5 Participants	78 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Week 6 of DBPC Cycle

Population: 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.

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.

Outcome measures

Measure	Placebo n=64 Participants 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.	Dysport® 600 U n=62 Participants 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.	Dysport® 800 U n=67 Participants 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.
Mean Change From Baseline in Weekly Number of UI Episodes at Week 6 of DBPC Cycle	-12.7 Weekly UI episodes Standard Error 2.01	-23.5 Weekly UI episodes Standard Error 2.04	-24.9 Weekly UI episodes Standard Error 1.97

SECONDARY outcome

Timeframe: Baseline and Week 6 of DBPC Cycle

Population: 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.

All subjects had a standardised urodynamic (filling cystometry) assessment at baseline (screening) and again at Week 6 to determine the MCC. The LS mean of the change in MCC at 6 weeks after the first study treatment was calculated using an analysis of covariance (ANCOVA).

Outcome measures

Measure	Placebo n=66 Participants 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.	Dysport® 600 U n=60 Participants 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.	Dysport® 800 U n=70 Participants 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.
Mean Change From Baseline in Maximum Cystometric Capacity (MCC) at Week 6 of DBPC Cycle	-8.5 mL Standard Error 18.06	152.4 mL Standard Error 19.10	180.7 mL Standard Error 17.70

SECONDARY outcome

Timeframe: Baseline and Week 6 of DBPC Cycle

Population: 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.

All subjects had a standardised urodynamic filling cystometry assessment at baseline (screening) and again at Week 6 to determine the MDP. The LS mean of the change in MDP at 6 weeks after the first study treatment was calculated using an ANCOVA.

Outcome measures

Measure	Placebo n=58 Participants 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.	Dysport® 600 U n=54 Participants 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.	Dysport® 800 U n=65 Participants 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.
Mean Change From Baseline in Maximum Detrusor Pressure (MDP) at Week 6 of DBPC Cycle	-5.4 centimetres of water Standard Error 2.83	-29.8 centimetres of water Standard Error 2.96	-34.1 centimetres of water Standard Error 2.71

SECONDARY outcome

Timeframe: Baseline and Week 6 of DBPC Cycle

Population: 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.

All subjects had a standardised urodynamic (filling cystometry) assessment at baseline (screening) and again at Week 6 to determine the Vol@1stIDC which is the instilled volume when first IDC commences. Subjects who did not exhibit a post-treatment IDC at Week 6 had Vol@1stIDC imputed using the recorded corrected MCC volume at Week 6. The LS mean of the change in Vol@1stIDC at 6 weeks after the first study treatment was calculated using an ANCOVA.

Outcome measures

Measure	Placebo n=63 Participants 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.	Dysport® 600 U n=56 Participants 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.	Dysport® 800 U n=66 Participants 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.
Mean Change From Baseline in Volume at First Involuntary Detrusor Contraction (Vol@1stIDC) at Week 6 of DBPC Cycle	14.0 mL Standard Error 19.45	169.4 mL Standard Error 20.72	195.7 mL Standard Error 19.12

SECONDARY outcome

Timeframe: Baseline and Week 6 of DBPC Cycle

Population: 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.

The weekly number of UI episodes was measured using a 7-day bladder diary. Bladder diaries that contained data recorded on at least 5 days were included in the analysis. The number of subjects with no UI episodes at 6 weeks after the first study treatment was recorded and the percentage of subjects was also calculated from the total number of subjects with any number of UI events at Week 6.

Outcome measures

Measure	Placebo n=64 Participants 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.	Dysport® 600 U n=62 Participants 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.	Dysport® 800 U n=67 Participants 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.
Number of Subjects With No Episodes of UI at Week 6 of DBPC Cycle	3 Participants	21 Participants	21 Participants

SECONDARY outcome

Timeframe: Baseline and Week 6 of DBPC Cycle

Population: 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.

All subjects had a standardised urodynamic filling cystometry assessment at baseline (screening) and again at Week 6 to determine the occurrence of IDCs. The number of subjects without IDCs at 6 weeks after the first study treatment was recorded and the percentage of subjects was also calculated from the total number of subjects with data available for analysis at Week 6.

Outcome measures

Measure	Placebo n=63 Participants 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.	Dysport® 600 U n=60 Participants 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.	Dysport® 800 U n=71 Participants 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.
Number of Subjects With No IDCs During Storage at Week 6 of DBPC Cycle	6 Participants	20 Participants	42 Participants

SECONDARY outcome

Timeframe: Baseline and Week 6 of DBPC Cycle

Population: 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.

The I-QoL questionnaire is a validated, disease-specific questionnaire designed to measure the effect of UI on subjects' QoL. It consists of 22 items in 3 domains (avoidance and limiting behaviour, psychosocial impact and social embarrassment). Subjects used a 5-point response scale for each of the 22 items with values ranging from 1 (extremely) to 5 (not at all). The total summary score was transformed to a 100 point scale ranging from 0 to 100, with higher scores indicating a better QoL. The LS mean of the change in the I-QoL total summary score at 6 weeks after the first study treatment was calculated using a MMRM analysis.

Outcome measures

Measure	Placebo n=71 Participants 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.	Dysport® 600 U n=61 Participants 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.	Dysport® 800 U n=68 Participants 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.
Mean Change From Baseline in Incontinence Quality of Life (I-QoL) Questionnaire Total Summary Score at Week 6 of DBPC Cycle	5.8 score on a scale Standard Error 2.52	19.1 score on a scale Standard Error 2.63	23.0 score on a scale Standard Error 2.51

SECONDARY outcome

Timeframe: Baseline and Week 6 of DBPC Cycle

Population: 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.

The weekly number of UI episodes was measured using a 7-day bladder diary. Bladder diaries that contained data recorded on at least 5 days were included in the analysis. The number of baseline UI episodes was compared with the number of UI episodes at Week 6 to determine the level of response each subject reached, i.e. a decrease of ≥30%, ≥50% or ≥75% . The number of subjects showing an improvement of ≥30%, ≥50% and ≥75% were recorded and the percentage of subjects was also calculated from the total number of subjects with any number of UI events at Week 6.

Outcome measures

Measure	Placebo n=64 Participants 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.	Dysport® 600 U n=62 Participants 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.	Dysport® 800 U n=67 Participants 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.
Number of Subjects With a UI Response at Improvement Levels ≥30%, ≥50%, and ≥75% at Week 6 of the DBPC Cycle ≥30% Improvement	32 Participants	50 Participants	52 Participants
Number of Subjects With a UI Response at Improvement Levels ≥30%, ≥50%, and ≥75% at Week 6 of the DBPC Cycle ≥50% Improvement	19 Participants	47 Participants	50 Participants
Number of Subjects With a UI Response at Improvement Levels ≥30%, ≥50%, and ≥75% at Week 6 of the DBPC Cycle ≥75% Improvement	9 Participants	39 Participants	44 Participants

SECONDARY outcome

Timeframe: Baseline and Week 6 of DBPC Cycle

Population: 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.

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.

Outcome measures

Measure	Placebo n=62 Participants 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.	Dysport® 600 U n=60 Participants 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.	Dysport® 800 U n=65 Participants 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.
Mean Change From Baseline in Volume Per Void at Week 6 of DBPC Cycle	2.3 mL Standard Error 14.92	87.1 mL Standard Error 15.10	112.8 mL Standard Error 14.50

SECONDARY outcome

Timeframe: Day of first treatment (baseline) and day of retreatment, up to 2 years

Population: mITT population: All randomised subjects who received at least 1 administration of study treatment. Subjects were analysed as randomised (planned treatment).

Duration of effect for time between treatments was calculated by: (the date of the first retreatment visit - date of first treatment administration in the DBPC cycle). The median number of days between treatments was determined based on the Kaplan-Meier method. Subjects with no retreatment were censored at the last visit.

Outcome measures

Measure	Placebo n=76 Participants 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.	Dysport® 600 U n=75 Participants 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.	Dysport® 800 U n=75 Participants 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.
Median Time Between Treatments	120.5 days Interval 44.0 to 616.0	215.0 days Interval 37.0 to 590.0	224.0 days Interval 82.0 to 647.0

Adverse Events

Placebo

Serious events: 8 serious events

Other events: 23 other events

Deaths: 0 deaths

Dysport® 600 U

Serious events: 9 serious events

Other events: 20 other events

Deaths: 0 deaths

Dysport® 800 U

Serious events: 6 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=76 participants at risk 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.	Dysport® 600 U n=73 participants at risk 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.	Dysport® 800 U n=77 participants at risk Subjects were administered Dysport® 800 U for 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.
Gastrointestinal disorders Ileus	0.00% 0/76 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	1.4% 1/73 • Number of events 1 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	0.00% 0/77 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.
General disorders Systemic inflammatory response syndrome	0.00% 0/76 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	1.4% 1/73 • Number of events 1 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	0.00% 0/77 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.
Infections and infestations Urinary tract infection	3.9% 3/76 • Number of events 3 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	4.1% 3/73 • Number of events 5 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	1.3% 1/77 • Number of events 1 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.
Infections and infestations Appendicitis	0.00% 0/76 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	0.00% 0/73 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	1.3% 1/77 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.
Infections and infestations Clostridium difficile infection	0.00% 0/76 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	0.00% 0/73 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	1.3% 1/77 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.
Infections and infestations Cystitis	0.00% 0/76 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	0.00% 0/73 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	1.3% 1/77 • Number of events 1 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.
Infections and infestations Epididymitis	0.00% 0/76 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	1.4% 1/73 • Number of events 1 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	0.00% 0/77 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.
Infections and infestations Erysipelas	0.00% 0/76 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	0.00% 0/73 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	1.3% 1/77 • Number of events 1 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.
Infections and infestations Osteomyelitis	0.00% 0/76 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	1.4% 1/73 • Number of events 1 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	0.00% 0/77 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.
Infections and infestations Pneumonia	1.3% 1/76 • Number of events 1 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	1.4% 1/73 • Number of events 1 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	0.00% 0/77 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.
Infections and infestations Bacteraemia	1.3% 1/76 • Number of events 1 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	0.00% 0/73 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	0.00% 0/77 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.
Infections and infestations Fournier's gangrene	1.3% 1/76 • Number of events 1 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	0.00% 0/73 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	0.00% 0/77 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.
Injury, poisoning and procedural complications Multiple injuries	0.00% 0/76 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	1.4% 1/73 • Number of events 1 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	0.00% 0/77 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/76 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	1.4% 1/73 • Number of events 1 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	0.00% 0/77 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.
Injury, poisoning and procedural complications Fibula fracture	1.3% 1/76 • Number of events 1 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	0.00% 0/73 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	0.00% 0/77 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.
Injury, poisoning and procedural complications Ligament sprain	1.3% 1/76 • Number of events 1 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	0.00% 0/73 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	0.00% 0/77 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.
Injury, poisoning and procedural complications Tibia fracture	2.6% 2/76 • Number of events 2 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	0.00% 0/73 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	0.00% 0/77 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/76 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	1.4% 1/73 • Number of events 1 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	0.00% 0/77 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.
Musculoskeletal and connective tissue disorders Muscular weakness	1.3% 1/76 • Number of events 1 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	0.00% 0/73 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	0.00% 0/77 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to abdominal cavity	0.00% 0/76 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	1.4% 1/73 • Number of events 1 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	0.00% 0/77 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.
Renal and urinary disorders Haematuria	0.00% 0/76 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	1.4% 1/73 • Number of events 1 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	1.3% 1/77 • Number of events 1 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.
Renal and urinary disorders Urethral stenosis	0.00% 0/76 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	1.4% 1/73 • Number of events 1 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	0.00% 0/77 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.
Reproductive system and breast disorders Uterine polyp	1.3% 1/76 • Number of events 1 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	0.00% 0/73 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	0.00% 0/77 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.
Vascular disorders Deep vein thrombosis	0.00% 0/76 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	0.00% 0/73 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	1.3% 1/77 • Number of events 1 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.
Vascular disorders Hypertension	0.00% 0/76 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	1.4% 1/73 • Number of events 1 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	0.00% 0/77 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/76 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	1.4% 1/73 • Number of events 1 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	0.00% 0/77 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.

Other adverse events

Measure	Placebo n=76 participants at risk 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.	Dysport® 600 U n=73 participants at risk 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.	Dysport® 800 U n=77 participants at risk Subjects were administered Dysport® 800 U for 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.
Gastrointestinal disorders Constipation	1.3% 1/76 • Number of events 1 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	2.7% 2/73 • Number of events 2 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	1.3% 1/77 • Number of events 1 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.
Gastrointestinal disorders Abdominal pain	3.9% 3/76 • Number of events 3 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	1.4% 1/73 • Number of events 1 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	0.00% 0/77 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.
General disorders Pyrexia	2.6% 2/76 • Number of events 2 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	2.7% 2/73 • Number of events 2 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	0.00% 0/77 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.
Infections and infestations Urinary tract infection	17.1% 13/76 • Number of events 26 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	17.8% 13/73 • Number of events 26 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	27.3% 21/77 • Number of events 27 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.
Infections and infestations Influenza	0.00% 0/76 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	0.00% 0/73 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	2.6% 2/77 • Number of events 2 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.
Infections and infestations Pharyngitis	0.00% 0/76 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	2.7% 2/73 • Number of events 2 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	0.00% 0/77 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.
Infections and infestations Nasopharyngitis	5.3% 4/76 • Number of events 4 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	1.4% 1/73 • Number of events 1 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	0.00% 0/77 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.
Nervous system disorders Paraesthesia	0.00% 0/76 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	2.7% 2/73 • Number of events 2 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	0.00% 0/77 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.
Nervous system disorders Dizziness	2.6% 2/76 • Number of events 2 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	1.4% 1/73 • Number of events 1 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	0.00% 0/77 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.
Renal and urinary disorders Haematuria	1.3% 1/76 • Number of events 1 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	4.1% 3/73 • Number of events 3 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	2.6% 2/77 • Number of events 2 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.
Renal and urinary disorders Dysuria	1.3% 1/76 • Number of events 1 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	2.7% 2/73 • Number of events 2 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	2.6% 2/77 • Number of events 2 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.
Reproductive system and breast disorders Erectile dysfunction	0.00% 0/76 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	2.7% 2/73 • Number of events 2 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.	0.00% 0/77 • Treatment emergent adverse events are presented for the full DBPC cycle (i.e. approximately 35 weeks for both Dysport® groups and approximately 25 weeks for the Placebo group). All cause mortality is presented for the duration of the study (up to a maximum of 113 weeks). 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. Two subjects randomised to the Dysport 600 U group in the DBPC cycle received Dysport 800 U and are therefore included in the Dysport 800 U group for the safety population.

Additional Information

Medical Director

Ipsen

Phone: See email

Email: clinical.trials@ipsen.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place