CONTENT1: Dysport® Treatment of Urinary Incontinence in Adults Subjects With Neurogenic Detrusor Overactivity (NDO) Due to Spinal Cord Injury or Multiple Sclerosis - Study 1

• Sponsor: Ipsen (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02660138
• Collaborator: (none)
• Enrollment: 227
• Locations: 81
• Arms: 4
• Duration (Months): 35.5
• Patients Per Site: 2.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to provide confirmatory evidence of the safety and efficacy of two Dysport® (AbobotulinumtoxinA) doses (600 units [U] and 800 U), compared to placebo in reducing urinary incontinence (UI) in adult subjects treated for neurogenic detrusor overactivity (NDO) due to spinal cord injury (SCI) or multiple sclerosis (MS).

Condition or Disease	Intervention/Treatment	Phase
Urinary Incontinence; Overactive Bladder	Biological: Botulinum toxin type A; Biological: Botulinum toxin type A; Drug: Placebo; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 227 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase III, Multicentre, Randomised, Double Blind, Parallel Group, Placebo Controlled Study To Assess The Efficacy And Safety Of One Or More Intradetrusor Treatments Of 600 Or 800 Units of Dysport® For The Treatment Of Urinary Incontinence In Subjects With Neurogenic Detrusor Overactivity Due To Spinal Cord Injury Or Multiple Sclerosis
• Study Start Date: Mar 1, 2016
• Actual Primary Completion Date: Nov 9, 2018
• Actual Study Completion Date: Feb 14, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 600 U Dysport® Group	Biological: Botulinum toxin type A; 600 U intra detrusor injection in two treatment periods (Initial and Retreatment phase) delivered at 30 injection points; Other Names: AbobotulinumtoxinA (Dysport®) Clostridium BTX-A-haemagglutinin complex
Placebo Comparator: 600 U Dysport® Placebo Group	Drug: Placebo; AbobotulinumtoxinA Placebo 600 U intra detrusor injection in two treatment periods (Initial and Retreatment phase) delivered at 30 injection points
Experimental: 800 U Dysport® Group	Biological: Botulinum toxin type A; 800 U intra detrusor injection in two treatment periods (Initial and Retreatment phase) delivered at 30 injection points; Other Names: AbobotulinumtoxinA (Dysport®) Clostridium BTX-A-haemagglutinin complex
Placebo Comparator: 800 U Dysport® Placebo Group	Drug: Placebo; AbobotulinumtoxinA Placebo 800 U intra detrusor injection in two treatment periods (Initial and Retreatment phase) delivered at 30 injection points

Outcome Measures

Primary Outcome Measures

1. Mean Change From Baseline in Weekly Number of UI Episodes at Week 6 of DBPC Cycle [Baseline and Week 6 of DBPC Cycle]

   The weekly number of UI episodes was measured using a 7-day bladder diary. Bladder diaries that contained data recorded on at least 5 days were included in the analysis. The least square (LS) mean of the change in weekly number of UI episodes at 6 weeks after the first study treatment was calculated using a mixed model repeated measures (MMRM) analysis.

Secondary Outcome Measures

1. Mean Change From Baseline in Maximum Cystometric Capacity (MCC) at Week 6 of DBPC Cycle [Baseline and Week 6 of DBPC Cycle]

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

2. Mean Change From Baseline in Maximum Detrusor Pressure (MDP) at Week 6 of DBPC Cycle [Baseline and Week 6 of DBPC Cycle]

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

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

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

4. Number of Subjects With No Episodes of UI at Week 6 of DBPC Cycle [Baseline and Week 6 of DBPC Cycle]

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

5. Number of Subjects With No IDCs During Storage at Week 6 of DBPC Cycle [Baseline and Week 6 of DBPC Cycle]

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

6. Mean Change From Baseline in Incontinence Quality of Life (I-QoL) Questionnaire Total Summary Score at Week 6 of DBPC Cycle [Baseline and Week 6 of DBPC Cycle]

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

7. Number of Subjects With a UI Response at Improvement Levels ≥30%, ≥50%, and ≥75% at Week 6 of the DBPC Cycle [Baseline and Week 6 of DBPC Cycle]

   The weekly number of UI episodes was measured using a 7-day bladder diary. Bladder diaries that contained data recorded on at least 5 days were included in the analysis. The number of 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.

8. Mean Change From Baseline in Volume Per Void at Week 6 of DBPC Cycle [Baseline and Week 6 of DBPC Cycle]

   The volume per void was measured during one 24-hour period of the 7-day bladder diary. The LS mean of the change in volume per void at 6 weeks after the first study treatment was calculated using a MMRM analysis.

9. Median Time Between Treatments [Day of first treatment (baseline) and day of retreatment, up to 2 years]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Urinary Incontinence for at least 3 months prior to Screening as a result of Neurogenic Detrusor Overactivity due to Spinal Cord Injury or Multiple Sclerosis.

• Subjects with Spinal Cord Injury must have a stable neurological injury at T1 level or below which occurred at least 6 months prior to Screening.

• Subjects with Multiple Sclerosis must be clinically stable in the investigator's opinion, with no exacerbation (relapse) of MS for at least 3 months prior to Screening.

• Subjects must have had an inadequate response after at least 4 weeks of oral medications used in the treatment of NDO (e.g. anticholinergics, beta-3 agonists) and/or have intolerable side-effects.

• Routinely performing Clean Intermittent Catheterization (CIC) to ensure adequate bladder emptying.

• An average of at least two episodes per day of Urinary Incontinence recorded on the screening bladder diary.

Key Exclusion Criteria:

• Any current condition (other than NDO) that may impact on bladder function.

• Previous or current, tumour or malignancy affecting the spinal column or spinal cord, or any other unstable cause of SCI.

• Any condition that will prevent cystoscopic treatment administration or CIC usage, e.g. urethral strictures.

• Current indwelling bladder catheter, or removal of indwelling bladder catheter less than 4 weeks prior to Screening.

• BTX-A treatment within 9 months prior to Screening for any urological condition (e.g. detrusor or urethral sphincter treatments).

• Any neuromodulation/electrostimulation usage for urinary symptoms/incontinence within 4 weeks prior to Screening. Any implanted neuromodulation device must be switched off at least 4 weeks prior to Screening.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UAB School of Medicine Spain Rehabilitation Center (SRC)	Birmingham	Alabama	United States	35249
2	Urological Associates of Southern Arizona, P.C.	Tucson	Arizona	United States	85715-3808
3	Atlantic Urology Medical Group	Long Beach	California	United States	90806
4	USC Norris Comprehensive Cancer Center	Los Angeles	California	United States	90089
5	UC Davis Medical Center	Sacramento	California	United States	95817-2307
6	University of Colorado Denver	Aurora	Colorado	United States	80045-2527
7	Women's Health Specialty Care	Farmington	Connecticut	United States	06032-1933
8	Gousse Urology - The Bladder Heath and Reconstructive Urology Institute	Miramar	Florida	United States	33029-5593
9	The Iowa Clinic, PC	West Des Moines	Iowa	United States	50266
10	Chesapeake Urology Associates, PA	Owings Mills	Maryland	United States	21117
11	University of Michigan Hospital	Ann Arbor	Michigan	United States	48109
12	Weill Cornell Medical College	Denville	New Jersey	United States	07834
13	Delaware Valley Urology,IIC	Voorhees	New Jersey	United States	08043
14	Urology Group of New Mexico, PC	Albuquerque	New Mexico	United States	87109
15	Montefiore Medical Center	Bronx	New York	United States	10461
16	New York University Langone Medical Center and School of Medicine	New York	New York	United States	10016
17	New York-Presbyterian Hospital/Weill Cornell Medical Center	New York	New York	United States	10065
18	Advanced Urology Centers of New York	Plainview	New York	United States	11783
19	University of North Carolina School of Medicine	Chapel Hill	North Carolina	United States	27599
20	Levine Cancer Institute	Charlotte	North Carolina	United States	28207
21	Louis Stokes Cleveland Veterans Affairs Medical Center	Cleveland	Ohio	United States	44106
22	Cleveland Clinic	Cleveland	Ohio	United States	44195
23	Lancaster Urology	Lancaster	Pennsylvania	United States	17601
24	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania	United States	19107
25	Medical University of South Carolina (MUSC)	Charleston	South Carolina	United States	29425
26	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
27	Urology Clinics of North Texas	Dallas	Texas	United States	75231
28	Houston Methodist Hospital	Houston	Texas	United States	77030
29	Lahey Hospital & Medical Center	Burlington	Vermont	United States	01805-0001
30	Urology of Virginia, PLLC	Virginia Beach	Virginia	United States	23462-1815
31	Integrity Medical Research	Mountlake Terrace	Washington	United States	98043
32	Medical College of Wisconsin - Freodert Hospital	Milwaukee	Wisconsin	United States	53226
33	CHUS - Hôpital Fleurimont	Sherbrooke		Canada	02114-2621
34	Sunnybrook Health Sciences Centre	Toronto		Canada	02115-6110
35	UBC Hospital - Koerner Pavilion	Vancouver		Canada	V6T 2B5
36	Spinal Cord Research Centre, University of Manitoba	Winnipeg		Canada	R3A 1M4
37	Fakultní Nemocnice Brno	Brno		Czechia	62500
38	Karlovarska krajska nemocnice, a.s.	Karlovy Vary		Czechia	360 01
39	Krajská Nemocnice Liberec, a.s.	Liberec		Czechia	46063
40	Uromedical Center s.r.o.	Olomouc		Czechia	77900
41	Fakultní nemocnice Královské Vinohrady	Praha 10		Czechia	100 34
42	Všeobecná fakultní nemocnice v Praze	Praha 2		Czechia	12808
43	Fakultní Nemocnice v Motole	Praha 5		Czechia	15006
44	Thomayerova nemocnice	Praha		Czechia	14059
45	Urologicka Ordinace s.r.o.	Sternberk		Czechia	785 01
46	Azienda Ospedaliero-Universitaria Careggi - Dipartimento Di Neuro-Urologia	Firenze		Italy	50134
47	Farmacia Istituto Ospedaliero ICOT "Marco Pasquali"	Latina		Italy	04100
48	Azienda Ospedaliera di Perugia - Ospedale Santa Maria della Misericordia	Perugia		Italy	06132
49	Viale Oxford, 81	Roma		Italy	00133
50	Ospedale "Bolognini" di Seriate	Seriate		Italy	24068
51	Azienda Ospedaliera di Perugia - Ospedale Santa Maria della Misericordia	Udine		Italy	33100
52	88 Olympic-ro 43-gil, Songpa-gu	Seoul		Korea, Republic of	05505
53	Samsung Medical Center	Seoul		Korea, Republic of	6351
54	Ulsan University Hospital (UUH)	Ulsan		Korea, Republic of	44033
55	VU University Medical Center	Amsterdam		Netherlands	1081 HV
56	Radboud UMC	Nijmegen		Netherlands	6525 GA
57	Erasmus MC	Rotterdam		Netherlands	3015 CE
58	Wojewódzki Szpital Zespolony w Elblągu	Elblag		Poland	82-300
59	Nzoz Neuro-Medic Poradnia Wielospecjalistyczna	Katowice		Poland	40-752
60	NZOZ Heureka	Piaseczno		Poland	05-500
61	Szpital Kliniczny Dzieciątka Jezus w Warszawie	Warszawa		Poland	02-005
62	EuroMediCare Szpital Specjalistyczny z Przychodnią we Wrocławiu	Wroclaw		Poland	54-144
63	Hospital de Braga	Braga		Portugal	4700-001
64	Centro Hospitalar do Alto Ave, EPE	Guimarães		Portugal	4835-044
65	British Hospital	Lisboa		Portugal	1600-209
66	Centro Hospitalar do Porto, EPE - Hospital Geral de Santo António	Porto		Portugal	4099-001
67	Centro Hospitalar de São João, EPE - Hospital de São João	Porto		Portugal	4200-319
68	Gnosis Evomed	Bucharest		Romania	031864
69	Spitalul Clinic Colentina	Bucharest		Romania	20125
70	Spitalul Clinic Fundeni Bucureşti	Bucharest		Romania	22328
71	Hifu Terramed Conformal S.R.L	Bucharest		Romania	31864
72	Spitalul Clinic Judeţean Mureş	Târgu-Mureş		Romania	540103
73	Ankara Üniversitesi Tıp Fakültesi	Ankara		Turkey	6100
74	Medipol Mega University Hospital	Bagcilar		Turkey	34200
75	Uludag Universitesi Tip Fakultesi, Uroloji Anabilim Dali, Gorukle	Bursa		Turkey	16059
76	Marmara Üniversitesi Eğitim ve Araştırma Hastanesi	Istanbul		Turkey	34670
77	Istanbul Medeniyet Universitesi Goztepe Egitim ve Arastirma Hastanesi Merdivenköy Mah	Istanbul		Turkey	34732
78	Erciyes Üniversitesi Tıp Fakültesi	Kayseri		Turkey	38039
79	Kocaeli Üniversitesi Tıp Fakültesi	Kocaeli		Turkey	41380
80	Celal Bayar Universitesi Hafsa Sultan Hastanesi	Manisa		Turkey	45040
81	Ondokuz Mayıs Üniversitesi Tıp Fakültesi	Samsun		Turkey	55139

Sponsors and Collaborators

• Ipsen

Investigators

• Study Director: Ipsen Medical Director, Ipsen

Study Documents (Full-Text)

• Study Protocol - Apr 16, 2018
• Statistical Analysis Plan - Sep 21, 2018

More Information

Publications

None provided.

• Responsible Party: Ipsen
• ClinicalTrials.gov Identifier: NCT02660138
• Other Study ID Numbers: D-FR-52120-222; 2015-003471-30
• First Posted: Jan 21, 2016
• Last Update Posted: Jul 20, 2021
• Last Verified: Jul 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Multiple Sclerosis; Spinal Cord Injuries; Urinary Incontinence; Enuresis; Urinary Bladder, Overactive; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA; Hemagglutinins

Study Results

Participant Flow

Recruitment Details

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.

Pre-assignment Detail

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.

Arm/Group Title	Placebo	Dysport® 600 U	Dysport® 800 U
Arm/Group Description	Subjects were administered placebo on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 millilitres (mL) divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.	Subjects were administered Dysport® 600 U on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.	Subjects were administered Dysport® 800 U on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.
Period Title: Overall Study
STARTED	76	76	75
Subjects Treated in DBPC Cycle	76	75	75
Subjects Entered in the Dysport Cycles	49	75	75
COMPLETED	6	2	3
NOT COMPLETED	70	74	72

Baseline Characteristics

Arm/Group Title	Placebo	Dysport® 600 U	Dysport® 800 U	Total
Arm/Group Description	Subjects were administered placebo on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.	Subjects were administered Dysport® 600 U 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.	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 of all reporting groups
Overall Participants	76	75	75	226
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	68 89.5%	71 94.7%	66 88%	205 90.7%
>=65 years	8 10.5%	4 5.3%	9 12%	21 9.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.9 (13.15)	43.0 (12.38)	46.8 (13.58)	45.3 (13.09)
Sex: Female, Male (Count of Participants)
Female	38 50%	27 36%	30 40%	95 42%
Male	38 50%	48 64%	45 60%	131 58%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	4 5.3%	2 2.7%	4 5.3%	10 4.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	4 5.3%	3 4%	4 5.3%	11 4.9%
White	65 85.5%	70 93.3%	64 85.3%	199 88.1%
More than one race	1 1.3%	0 0%	0 0%	1 0.4%
Unknown or Not Reported	2 2.6%	0 0%	3 4%	5 2.2%
Aetiology of NDO (Count of Participants)
SCI	51 67.1%	49 65.3%	48 64%	148 65.5%
MS	25 32.9%	26 34.7%	27 36%	78 34.5%

Outcome Measures

1. Primary Outcome

Title	Mean Change From Baseline in Weekly Number of UI Episodes at Week 6 of DBPC Cycle
Description	The weekly number of UI episodes was measured using a 7-day bladder diary. Bladder diaries that contained data recorded on at least 5 days were included in the analysis. The least square (LS) mean of the change in weekly number of UI episodes at 6 weeks after the first study treatment was calculated using a mixed model repeated measures (MMRM) analysis.
Time Frame	Baseline and Week 6 of DBPC Cycle

Outcome Measure Data

Analysis Population Description

mITT population: All randomised subjects who received at least 1 administration of study treatment. Subjects were analysed as randomised (planned treatment). Only subjects with data available for analysis at Week 6 of DBPC cycle are presented.

Arm/Group Title	Placebo	Dysport® 600 U	Dysport® 800 U
Arm/Group Description	Subjects were administered placebo on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.	Subjects were administered Dysport® 600 U on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.	Subjects were administered Dysport® 800 U on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.
Measure Participants	64	62	67
Least Squares Mean (Standard Error) [Weekly UI episodes]	-12.7 (2.01)	-23.5 (2.04)	-24.9 (1.97)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dysport® 600 U
	Comments	Treatment group, visit (Week 2, Week 6 and Week 12), treatment-by-visit interaction, recorded stratification factors (aetiology of NDO [SCI or MS], prior intradetrusor [Botulinum toxin [BTX]-naïve or BTX-non-naïve]) and study baseline value (weekly number of UI episodes) as fixed effect variables, and subject as a random effect.
	Type of Statistical Test	Superiority
	Comments	If both p-values for the 2 primary tests (the test of Dysport® 800 U vs. placebo and the test of Dysport® 600 U vs. placebo) were lower than 0.05, both were declared statistically significant. If 1 of the primary tests had a p-value greater than or equal to 0.05, then the other test was declared statistically significant if its p-value was lower than 0.025.
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-10.83
	Confidence Interval	(2-Sided) 95%; -16.36 to -5.31
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dysport® 800 U
	Comments	Treatment group, visit (Week 2, Week 6 and Week 12), treatment-by-visit interaction, recorded stratification factors (aetiology of NDO [SCI or MS], prior intradetrusor [BTX-naïve or BTX-non-naïve]) and study baseline value (weekly number of UI episodes) as fixed effect variables, and subject as a random effect.
	Type of Statistical Test	Superiority
	Comments	If both p-values for the 2 primary tests (the test of Dysport® 800 U vs. placebo and the test of Dysport® 600 U vs. placebo) were lower than 0.05, both were declared statistically significant. If 1 of the primary tests had a p-value greater than or equal to 0.05, then the other test was declared statistically significant if its p-value was lower than 0.025.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-12.19
	Confidence Interval	(2-Sided) 95%; -17.65 to -6.73
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

mITT population: All randomised subjects who received at least 1 administration of study treatment. Subjects were analysed as randomised (planned treatment). Only subjects with data available for analysis at Week 6 of DBPC cycle are presented.

Arm/Group Title	Placebo	Dysport® 600 U	Dysport® 800 U
Arm/Group Description	Subjects were administered placebo on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.	Subjects were administered Dysport® 600 U on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.	Subjects were administered Dysport® 800 U on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.
Measure Participants	66	60	70
Least Squares Mean (Standard Error) [mL]	-8.5 (18.06)	152.4 (19.10)	180.7 (17.70)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dysport® 600 U
	Comments	Treatment group, recorded stratification factors (aetiology of NDO [SCI or MS], prior intradetrusor [BTX-naïve or BTX-non-naïve]) and baseline value of MCC as covariates.
	Type of Statistical Test	Superiority
	Comments	This secondary endpoint was included in the hierarchical analysis and was tested for both doses at the 0.05 level using a hierarchical methodology.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	160.9
	Confidence Interval	(2-Sided) 95%; 109.9 to 211.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dysport® 800 U
	Comments	Treatment group, recorded stratification factors (aetiology of NDO [SCI or MS], prior intradetrusor [BTX-naïve or BTX-non-naïve]) and baseline value of MCC as covariates.
	Type of Statistical Test	Superiority
	Comments	This secondary endpoint was included in the hierarchical analysis and was tested for both doses at the 0.05 level using a hierarchical methodology.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	189.2
	Confidence Interval	(2-Sided) 95%; 140.1 to 238.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

mITT population: All randomised subjects who received at least 1 administration of study treatment. Subjects were analysed as randomised (planned treatment). Only subjects with data available for analysis at Week 6 of DBPC cycle are presented.

Arm/Group Title	Placebo	Dysport® 600 U	Dysport® 800 U
Arm/Group Description	Subjects were administered placebo on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.	Subjects were administered Dysport® 600 U 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.	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.
Measure Participants	58	54	65
Least Squares Mean (Standard Error) [centimetres of water]	-5.4 (2.83)	-29.8 (2.96)	-34.1 (2.71)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dysport® 600 U
	Comments	Treatment group, recorded stratification factors (aetiology of NDO [SCI or MS], prior intradetrusor [BTX-naïve or BTX-non-naïve]) and baseline value of MDP as covariates.
	Type of Statistical Test	Superiority
	Comments	This secondary endpoint was included in the hierarchical analysis and was tested for both doses at the 0.05 level using a hierarchical methodology.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-24.3
	Confidence Interval	(2-Sided) 95%; -32.3 to -16.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dysport® 800 U
	Comments	Treatment group, recorded stratification factors (aetiology of NDO [SCI or MS], prior intradetrusor [BTX-naïve or BTX-non-naïve]) and baseline value of MDP as covariates.
	Type of Statistical Test	Superiority
	Comments	This secondary endpoint was included in the hierarchical analysis and was tested for both doses at the 0.05 level using a hierarchical methodology.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-28.6
	Confidence Interval	(2-Sided) 95%; -36.2 to -21.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

mITT population: All randomised subjects who received at least 1 administration of study treatment. Subjects were analysed as randomised (planned treatment). Only subjects with data available for analysis at Week 6 of DBPC cycle are presented.

Arm/Group Title	Placebo	Dysport® 600 U	Dysport® 800 U
Arm/Group Description	Subjects were administered placebo on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.	Subjects were administered Dysport® 600 U on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.	Subjects were administered Dysport® 800 U on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.
Measure Participants	63	56	66
Least Squares Mean (Standard Error) [mL]	14.0 (19.45)	169.4 (20.72)	195.7 (19.12)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dysport® 600 U
	Comments	Treatment group, recorded stratification factors (aetiology of NDO [SCI or MS], prior intradetrusor [BTX-naïve or BTX-non-naïve]) and baseline value of Vol@1stIDC as covariates.
	Type of Statistical Test	Superiority
	Comments	This secondary endpoint was included in the hierarchical analysis and was tested for both doses at the 0.05 level using a hierarchical methodology.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	155.5
	Confidence Interval	(2-Sided) 95%; 100.5 to 210.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dysport® 800 U
	Comments	Treatment group, recorded stratification factors (aetiology of NDO [SCI or MS], prior intradetrusor [BTX-naïve or BTX-non-naïve]) and baseline value of Vol@1stIDC as covariates.
	Type of Statistical Test	Superiority
	Comments	This secondary endpoint was included in the hierarchical analysis and was tested for both doses at the 0.05 level using a hierarchical methodology.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	181.8
	Confidence Interval	(2-Sided) 95%; 129.2 to 234.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

mITT population: All randomised subjects who received at least 1 administration of study treatment . Subjects were analysed as randomised (planned treatment). Only subjects with data available for analysis at Week 6 of DBPC cycle are presented.

Arm/Group Title	Placebo	Dysport® 600 U	Dysport® 800 U
Arm/Group Description	Subjects were administered placebo on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.	Subjects were administered Dysport® 600 U on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.	Subjects were administered Dysport® 800 U 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.
Measure Participants	64	62	67
Count of Participants [Participants]	3 3.9%	21 28%	21 28%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dysport® 600 U
	Comments	Treatment group, recorded stratification factors, visit (Week 2, Week 6 and Week 12), treatment-by-visit interaction, study baseline-by-visit interaction and study baseline weekly number of UI episodes as fixed effect.
	Type of Statistical Test	Superiority
	Comments	This secondary endpoint was included in the hierarchical analysis and was tested for both doses at the 0.05 level using a hierarchical methodology.
Statistical Test of Hypothesis	p-Value	0.0006
	Comments
	Method	Generalised linear mixed model (GLMM)
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	9.83
	Confidence Interval	(2-Sided) 95%; 2.72 to 35.60
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dysport® 800 U
	Comments	Treatment group, recorded stratification factors, visit (Week 2, Week 6 and Week 12), treatment-by-visit interaction, study baseline-by-visit interaction and study baseline weekly number of UI episodes as fixed effect.
	Type of Statistical Test	Superiority
	Comments	This secondary endpoint was included in the hierarchical analysis and was tested for both doses at the 0.05 level using a hierarchical methodology.
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	GLMM
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	10.99
	Confidence Interval	(2-Sided) 95%; 3.05 to 39.61
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Number of Subjects With No IDCs During Storage at Week 6 of DBPC Cycle
Description	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.
Time Frame	Baseline and Week 6 of DBPC Cycle

Outcome Measure Data

Analysis Population Description

mITT population: All randomised subjects who received at least 1 administration of study treatment. Subjects were analysed as randomised (planned treatment). Only subjects with data available for analysis at Week 6 of DBPC cycle are presented.

Arm/Group Title	Placebo	Dysport® 600 U	Dysport® 800 U
Arm/Group Description	Subjects were administered placebo on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.	Subjects were administered Dysport® 600 U on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.	Subjects were administered Dysport® 800 U on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.
Measure Participants	63	60	71
Count of Participants [Participants]	6 7.9%	20 26.7%	42 56%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dysport® 600 U
	Comments	Treatment group, and recorded stratification factors (aetiology of NDO, previous BTX-A usage) and study baseline (prior intradetrusor BTX-A usage for UI) as explanatory variables.
	Type of Statistical Test	Superiority
	Comments	This secondary endpoint was included in the hierarchical analysis and was tested for both doses at the 0.05 level using a hierarchical methodology.
Statistical Test of Hypothesis	p-Value	0.0010
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	5.73
	Confidence Interval	(2-Sided) 95%; 2.02 to 16.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dysport® 800 U
	Comments	Treatment group, and recorded stratification factors (aetiology of NDO, previous BTX-A usage) and study baseline (prior intradetrusor BTX-A usage for UI) as explanatory variables.
	Type of Statistical Test	Superiority
	Comments	This secondary endpoint was included in the hierarchical analysis and was tested for both doses at the 0.05 level using a hierarchical methodology.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	16.08
	Confidence Interval	(2-Sided) 95%; 5.82 to 44.43
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Mean Change From Baseline in Incontinence Quality of Life (I-QoL) Questionnaire Total Summary Score at Week 6 of DBPC Cycle
Description	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.
Time Frame	Baseline and Week 6 of DBPC Cycle

Outcome Measure Data

Analysis Population Description

mITT population: All randomised subjects who received at least 1 administration of study treatment. Subjects were analysed as randomised (planned treatment). Only subjects with data available for analysis at Week 6 of DBPC cycle are presented.

Arm/Group Title	Placebo	Dysport® 600 U	Dysport® 800 U
Arm/Group Description	Subjects were administered placebo on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.	Subjects were administered Dysport® 600 U on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.	Subjects were administered Dysport® 800 U on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.
Measure Participants	71	61	68
Least Squares Mean (Standard Error) [score on a scale]	5.8 (2.52)	19.1 (2.63)	23.0 (2.51)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dysport® 600 U
	Comments	Treatment group, visit (Week 6 and Week 12), treatment-by-visit interaction, recorded stratification factors (aetiology of NDO [SCI or MS], prior intradetrusor [BTX-naïve or BTX-non-naïve]) and study baseline value (I-QoL summary total score) as fixed variables, and subject as a random effect.
	Type of Statistical Test	Superiority
	Comments	This secondary endpoint was included in the hierarchical analysis and was tested for both doses at the 0.05 level using a hierarchical methodology.
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	13.30
	Confidence Interval	(2-Sided) 95%; 6.22 to 20.37
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dysport® 800 U
	Comments	Treatment group, visit (Week 6 and Week 12), treatment-by-visit interaction, recorded stratification factors (aetiology of NDO [SCI or MS], prior intradetrusor [BTX-naïve or BTX-non-naïve]) and study baseline value (I-QoL summary total score) as fixed variables, and subject as a random effect.
	Type of Statistical Test	Superiority
	Comments	The secondary endpoint was included in the hierarchical analysis and was tested for both doses at the 0.05 level using a hierarchical methodology.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	17.25
	Confidence Interval	(2-Sided) 95%; 10.36 to 24.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Number of Subjects With a UI Response at Improvement Levels ≥30%, ≥50%, and ≥75% at Week 6 of the DBPC Cycle
Description	The weekly number of UI episodes was measured using a 7-day bladder diary. Bladder diaries that contained data recorded on at least 5 days were included in the analysis. The 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.
Time Frame	Baseline and Week 6 of DBPC Cycle

Outcome Measure Data

Analysis Population Description

mITT population: All randomised subjects who received at least 1 administration of study treatment . Subjects were analysed as randomised (planned treatment). Only subjects with data available for analysis at Week 6 of DBPC cycle are presented.

Arm/Group Title	Placebo	Dysport® 600 U	Dysport® 800 U
Arm/Group Description	Subjects were administered placebo on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.	Subjects were administered Dysport® 600 U on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.	Subjects were administered Dysport® 800 U on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.
Measure Participants	64	62	67
≥30% Improvement	32 42.1%	50 66.7%	52 69.3%
≥50% Improvement	19 25%	47 62.7%	50 66.7%
≥75% Improvement	9 11.8%	39 52%	44 58.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dysport® 600 U
	Comments	Treatment comparison at ≥30% Improvement Level: Dysport® 600 U versus Placebo.
	Type of Statistical Test	Superiority
	Comments	Treatment group, recorded stratification factors, visit (Week 2, Week 6 and Week 12), treatment-by-visit interaction, study baseline-by-visit interaction and study baseline weekly number of UI episodes as fixed effect.
Statistical Test of Hypothesis	p-Value	0.0007
	Comments	This secondary endpoint was not included within the hierarchical testing procedure and was analysed for exploratory purposes only to compare each Dysport® dose to placebo at a 0.05 type one error rate.
	Method	GLMM
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	4.00
	Confidence Interval	(2-Sided) 95%; 1.80 to 8.86
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dysport® 800 U
	Comments	Treatment comparison at ≥30% Improvement Level: Dysport® 800 U versus Placebo
	Type of Statistical Test	Superiority
	Comments	Treatment group, recorded stratification factors, visit (Week 2, Week 6 and Week 12), treatment-by-visit interaction, study baseline-by-visit interaction and study baseline weekly number of UI episodes as fixed effect.
Statistical Test of Hypothesis	p-Value	0.0012
	Comments	This secondary endpoint was not included within the hierarchical testing procedure and was analysed for exploratory purposes only to compare each Dysport® dose to placebo at a 0.05 type one error rate.
	Method	GLMM
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.63
	Confidence Interval	(2-Sided) 95%; 1.68 to 7.86
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dysport® 600 U
	Comments	Treatment comparison at ≥50% Improvement Level: Dysport® 600 U versus Placebo.
	Type of Statistical Test	Superiority
	Comments	Treatment group, recorded stratification factors, visit (Week 2, Week 6 and Week 12), treatment-by-visit interaction, study baseline-by-visit interaction and study baseline weekly number of UI episodes as fixed effect.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	This secondary endpoint was not included within the hierarchical testing procedure and was analysed for exploratory purposes only to compare each Dysport® dose to placebo at a 0.05 type one error rate.
	Method	GLMM
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	8.03
	Confidence Interval	(2-Sided) 95%; 3.56 to 18.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dysport® 800 U
	Comments	Treatment comparison at ≥50% Improvement Level: Dysport® 800 U versus Placebo
	Type of Statistical Test	Superiority
	Comments	Treatment group, recorded stratification factors, visit (Week 2, Week 6 and Week 12), treatment-by-visit interaction, study baseline-by-visit interaction and study baseline weekly number of UI episodes as fixed effect.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	This secondary endpoint was not included within the hierarchical testing procedure and was analysed for exploratory purposes only to compare each Dysport® dose to placebo at a 0.05 type one error rate.
	Method	GLMM
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	8.22
	Confidence Interval	(2-Sided) 95%; 3.66 to 18.47
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dysport® 600 U
	Comments	Treatment comparison at ≥75% Improvement Level: Dysport® 600 U versus Placebo.
	Type of Statistical Test	Other
	Comments	Treatment group, recorded stratification factors, visit (Week 2, Week 6 and Week 12), treatment-by-visit interaction, study baseline-by-visit interaction and study baseline weekly number of UI episodes as fixed effect.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	This secondary endpoint was not included within the hierarchical testing procedure and was analysed for exploratory purposes only to compare each Dysport® dose to placebo at a 0.05 type one error rate.
	Method	GLMM
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	10.70
	Confidence Interval	(2-Sided) 95%; 4.59 to 24.95
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dysport® 800 U
	Comments	Treatment comparison at ≥75% Improvement Level: Dysport® 800 U versus Placebo.
	Type of Statistical Test	Superiority
	Comments	Treatment group, recorded stratification factors, visit (Week 2, Week 6 and Week 12), treatment-by-visit interaction, study baseline-by-visit interaction and study baseline weekly number of UI episodes as fixed effect.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	This secondary endpoint was not included within the hierarchical testing procedure and was analysed for exploratory purposes only to compare each Dysport® dose to placebo at a 0.05 type one error rate.
	Method	GLMM
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	12.63
	Confidence Interval	(2-Sided) 95%; 5.40 to 29.56
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Mean Change From Baseline in Volume Per Void at Week 6 of DBPC Cycle
Description	The volume per void was measured during one 24-hour period of the 7-day bladder diary. The LS mean of the change in volume per void at 6 weeks after the first study treatment was calculated using a MMRM analysis.
Time Frame	Baseline and Week 6 of DBPC Cycle

Outcome Measure Data

Analysis Population Description

mITT population: All randomised subjects who received at least 1 administration of study treatment. Subjects were analysed as randomised (planned treatment). Only subjects with data available for analysis at Week 6 of DBPC cycle are presented.

Arm/Group Title	Placebo	Dysport® 600 U	Dysport® 800 U
Arm/Group Description	Subjects were administered placebo on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.	Subjects were administered Dysport® 600 U on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.	Subjects were administered Dysport® 800 U on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.
Measure Participants	62	60	65
Least Squares Mean (Standard Error) [mL]	2.3 (14.92)	87.1 (15.10)	112.8 (14.50)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dysport® 600 U
	Comments	Treatment group, visit (Week 2, Week 6 and Week 12), treatment-by-visit interaction, recorded stratification factors (aetiology of NDO [SCI or MS], prior intradetrusor [BTX-naïve or BTX-non-naïve]) and study baseline value (total volume per void) as fixed effect variables, and subject as a random effect.
	Type of Statistical Test	Superiority
	Comments	This secondary endpoint was not included within the hierarchical testing procedure and was analysed for exploratory purposes only to compare each Dysport® dose to placebo at a 0.05 type one error rate.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	84.81
	Confidence Interval	(2-Sided) 95%; 43.73 to 125.89
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dysport® 800 U
	Comments	Treatment group, visit (Week 2, Week 6 and Week 12), treatment-by-visit interaction, recorded stratification factors (aetiology of NDO [SCI or MS], prior intradetrusor [BTX-naïve or BTX-non-naïve]) and study baseline value (total volume per void) as fixed effect variables, and subject as a random effect.
	Type of Statistical Test	Superiority
	Comments	This secondary endpoint was not included within the hierarchical testing procedure and was analysed for exploratory purposes only to compare each Dysport® dose to placebo at a 0.05 type one error rate.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	110.57
	Confidence Interval	(2-Sided) 95%; 70.17 to 150.98
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Median Time Between Treatments
Description	Duration of effect for time between treatments was calculated by: (the date of the first retreatment visit - date of first treatment administration in the DBPC cycle). The median number of days between treatments was determined based on the Kaplan-Meier method. Subjects with no retreatment were censored at the last visit.
Time Frame	Day of first treatment (baseline) and day of retreatment, up to 2 years

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Dysport® 600 U	Dysport® 800 U
Arm/Group Description	Subjects were administered placebo on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.	Subjects were administered Dysport® 600 U on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.	Subjects were administered Dysport® 800 U on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.
Measure Participants	76	75	75
Median (Full Range) [days]	120.5	215.0	224.0

Adverse Events

Time Frame	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).
Adverse Event Reporting Description	The safety population included all subjects who received at least 1 administration of study treatment (including only partial administration). Safety subjects were analysed according to their actual treatment received. 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.
Arm/Group Title	Placebo		Dysport® 600 U		Dysport® 800 U
Arm/Group Description	Subjects were administered placebo on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.		Subjects were administered Dysport® 600 U on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each. Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required.		Subjects were administered Dysport® 800 U 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.
All Cause Mortality
	Placebo		Dysport® 600 U		Dysport® 800 U
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/76 (0%)		0/73 (0%)		0/77 (0%)
Serious Adverse Events
	Placebo		Dysport® 600 U		Dysport® 800 U
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/76 (10.5%)		9/73 (12.3%)		6/77 (7.8%)
Gastrointestinal disorders
Ileus	0/76 (0%)	0	1/73 (1.4%)	1	0/77 (0%)	0
General disorders
Systemic inflammatory response syndrome	0/76 (0%)	0	1/73 (1.4%)	1	0/77 (0%)	0
Infections and infestations
Urinary tract infection	3/76 (3.9%)	3	3/73 (4.1%)	5	1/77 (1.3%)	1
Appendicitis	0/76 (0%)		0/73 (0%)		1/77 (1.3%)
Clostridium difficile infection	0/76 (0%)	0	0/73 (0%)	0	1/77 (1.3%)	0
Cystitis	0/76 (0%)	0	0/73 (0%)	0	1/77 (1.3%)	1
Epididymitis	0/76 (0%)	0	1/73 (1.4%)	1	0/77 (0%)	0
Erysipelas	0/76 (0%)	0	0/73 (0%)	0	1/77 (1.3%)	1
Osteomyelitis	0/76 (0%)	0	1/73 (1.4%)	1	0/77 (0%)	0
Pneumonia	1/76 (1.3%)	1	1/73 (1.4%)	1	0/77 (0%)	0
Bacteraemia	1/76 (1.3%)	1	0/73 (0%)	0	0/77 (0%)	0
Fournier's gangrene	1/76 (1.3%)	1	0/73 (0%)	0	0/77 (0%)	0
Injury, poisoning and procedural complications
Multiple injuries	0/76 (0%)	0	1/73 (1.4%)	1	0/77 (0%)	0
Road traffic accident	0/76 (0%)	0	1/73 (1.4%)	1	0/77 (0%)	0
Fibula fracture	1/76 (1.3%)	1	0/73 (0%)	0	0/77 (0%)	0
Ligament sprain	1/76 (1.3%)	1	0/73 (0%)	0	0/77 (0%)	0
Tibia fracture	2/76 (2.6%)	2	0/73 (0%)	0	0/77 (0%)	0
Metabolism and nutrition disorders
Hypokalaemia	0/76 (0%)	0	1/73 (1.4%)	1	0/77 (0%)	0
Musculoskeletal and connective tissue disorders
Muscular weakness	1/76 (1.3%)	1	0/73 (0%)	0	0/77 (0%)	0
Arthralgia	0/76 (0%)	0	1/73 (1.4%)	1	0/77 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to abdominal cavity	0/76 (0%)	0	1/73 (1.4%)	1	0/77 (0%)	0
Renal and urinary disorders
Haematuria	0/76 (0%)	0	1/73 (1.4%)	1	1/77 (1.3%)	1
Urethral stenosis	0/76 (0%)	0	1/73 (1.4%)	1	0/77 (0%)	0
Reproductive system and breast disorders
Uterine polyp	1/76 (1.3%)	1	0/73 (0%)	0	0/77 (0%)	0
Vascular disorders
Deep vein thrombosis	0/76 (0%)	0	0/73 (0%)	0	1/77 (1.3%)	1
Hypertension	0/76 (0%)	0	1/73 (1.4%)	1	0/77 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		Dysport® 600 U		Dysport® 800 U
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/76 (30.3%)		20/73 (27.4%)		23/77 (29.9%)
Gastrointestinal disorders
Constipation	1/76 (1.3%)	1	2/73 (2.7%)	2	1/77 (1.3%)	1
Abdominal pain	3/76 (3.9%)	3	1/73 (1.4%)	1	0/77 (0%)	0
General disorders
Pyrexia	2/76 (2.6%)	2	2/73 (2.7%)	2	0/77 (0%)	0
Infections and infestations
Urinary tract infection	13/76 (17.1%)	26	13/73 (17.8%)	26	21/77 (27.3%)	27
Influenza	0/76 (0%)	0	0/73 (0%)	0	2/77 (2.6%)	2
Pharyngitis	0/76 (0%)	0	2/73 (2.7%)	2	0/77 (0%)	0
Nasopharyngitis	4/76 (5.3%)	4	1/73 (1.4%)	1	0/77 (0%)	0
Nervous system disorders
Paraesthesia	0/76 (0%)	0	2/73 (2.7%)	2	0/77 (0%)	0
Dizziness	2/76 (2.6%)	2	1/73 (1.4%)	1	0/77 (0%)	0
Renal and urinary disorders
Haematuria	1/76 (1.3%)	1	3/73 (4.1%)	3	2/77 (2.6%)	2
Dysuria	1/76 (1.3%)	1	2/73 (2.7%)	2	2/77 (2.6%)	2
Reproductive system and breast disorders
Erectile dysfunction	0/76 (0%)	0	2/73 (2.7%)	2	0/77 (0%)	0

Limitations/Caveats

This study was terminated early by the sponsor on 01 October 2018, due to low subject recruitment.

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Certain Agreements

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

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