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Clinical Trial Results:
Long-term Extension Study of BOTOX® in the Treatment of Urinary Incontinence Due to Neurogenic Detrusor Overactivity in Patients 5 to 17 Years of Age

Summary
EudraCT number	2012-004898-30
Trial protocol	BE CZ AT IT DE PL FR
Global end of trial date	03 Oct 2019

Results information
Results version number	v1(current)
This version publication date	19 Apr 2020
First version publication date	19 Apr 2020
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

191622-121

ISRCTN number

US NCT number

NCT01852058

WHO universal trial number (UTN)

Sponsor organisation name

Allergan plc

Sponsor organisation address

1st Floor, Marlow International, The Parkway, Marlow Buckinghamshire, United Kingdom, SL7 1YL

Public contact

Clinical Trials Registry Team, Allergan plc, 001 877‐277‐8566, IR-CTRegistration@allergan.com

Scientific contact

Therapeutic Area, Head, Allergan plc, 001 862-261-7000, IR-CTRegistration@Allergan.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

03 Oct 2019

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

03 Oct 2019

Was the trial ended prematurely?

Main objective of the trial

The main objective of this trial is to evaluate the long-term safety and efficacy of onabotulinumtoxinA (botulinum toxin Type A; BOTOX®) for the treatment of urinary incontinence due to neurogenic detrusor overactivity in participants who successfully completed Study 191622-120 (NCT01852045).

Protection of trial subjects

All study participants were required to read and sign an Informed Consent Form.

Background therapy

Evidence for comparator

Actual start date of recruitment

11 Jan 2014

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Belgium: 13

Country: Number of subjects enrolled

Czech Republic: 5

Country: Number of subjects enrolled

France: 11

Country: Number of subjects enrolled

Italy: 5

Country: Number of subjects enrolled

Poland: 22

Country: Number of subjects enrolled

Canada: 2

Country: Number of subjects enrolled

Turkey: 2

Country: Number of subjects enrolled

United States: 35

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Participants who successfully completed Study 191622-120 (NCT01852045) were enrolled in this study and were followed for up to an additional 60 weeks.

Screening details

Data from the participant's participation in this extension Study 191622-121 (121) were integrated with the corresponding participant's data from the preceding Study 191622-120 (120).

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

OnabotulinumtoxinA 50 U

Arm description

Following treatment with onabotulinumtoxinA (botulinum toxin Type A) 50 U (not to exceed 6 U/kg) intramuscular injection into the detrusor wall in Study 120, participants were eligible for retreatments in this study as needed with a minimum 12-week interval between doses for a maximum of 3 retreatments. Blinded dose increases (one level) were allowed based on clinical response from cycle to cycle (not to exceed 6 U/kg).

Arm type

Experimental

Investigational medicinal product name

OnabotulinumtoxinA

Investigational medicinal product code

Other name

BOTOX® botulinum toxin Type A

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

OnabotulinumtoxinA injected into the detrusor wall. Treatments were administered as needed with a minimum of a 12-week interval between doses.

OnabotulinumtoxinA 100 U

Arm description

Following treatment with onabotulinumtoxinA (botulinum toxin Type A) 100 U (not to exceed 6 U/kg) intramuscular injection into the detrusor wall in Study 120, participants were eligible for retreatments in this study as needed with a minimum 12-week interval between doses for a maximum of 3 retreatments. Blinded dose increases (one level) were allowed based on clinical response from cycle to cycle (not to exceed 6 U/kg).

Arm type

Experimental

Investigational medicinal product name

OnabotulinumtoxinA

Investigational medicinal product code

Other name

BOTOX® botulinum toxin Type A

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

OnabotulinumtoxinA injected into the detrusor wall. Treatments were administered as needed with a minimum of a 12-week interval between doses.

OnabotulinumtoxinA 200 U

Arm description

Following treatment with onabotulinumtoxinA (botulinum toxin Type A) 200 U (not to exceed 6 U/kg) intramuscular injection into the detrusor wall in Study 120, participants were eligible for retreatments in this study as needed with a minimum 12-week interval between doses for a maximum of 3 retreatments. Blinded dose increases (one level) were allowed based on clinical response from cycle to cycle (not to exceed 6 U/kg).

Arm type

Experimental

Investigational medicinal product name

OnabotulinumtoxinA

Investigational medicinal product code

Other name

BOTOX® botulinum toxin Type A

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

OnabotulinumtoxinA injected into the detrusor wall. Treatments were administered as needed with a minimum of a 12-week interval between doses.

Number of subjects in period 1	OnabotulinumtoxinA 50 U	OnabotulinumtoxinA 100 U	OnabotulinumtoxinA 200 U
Started	31	39	25
Completed	22	36	17
Not completed	9	3	8
Adverse event, non-fatal	1	-	-
Protocol Deviation	1	-	-
Withdrawal by Subject	3	1	1
Lost to follow-up	2	-	-
Reason not Specified	1	2	6
Lack of efficacy	1	-	1

Baseline characteristics

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Reporting group title

OnabotulinumtoxinA 50 U

Reporting group description

Reporting group title

OnabotulinumtoxinA 100 U

Reporting group description

Reporting group title

OnabotulinumtoxinA 200 U

Reporting group description

Reporting group values	OnabotulinumtoxinA 50 U	OnabotulinumtoxinA 100 U	OnabotulinumtoxinA 200 U	Total
Number of subjects	31	39	25	95
Age categorical
Units: Subjects
Children (2-11 years)	15	22	10	47
Adolescents (12-17 years)	16	17	15	48
Age Continuous
Units: years
arithmetic mean (standard deviation)	11.7 ± 3.49	10.8 ± 3.36	11.7 ± 3.22	-
Sex: Female, Male
Units: participants
Female	17	14	13	44
Male	14	25	12	51
Race/Ethnicity, Customized
Units: Subjects
White	22	28	18	68
Black or African American	6	3	2	11
Asian	1	2	0	3
Hispanic	1	3	3	7
Other	1	3	2	6

End points

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Reporting group title

OnabotulinumtoxinA 50 U

Reporting group description

Reporting group title

OnabotulinumtoxinA 100 U

Reporting group description

Reporting group title

OnabotulinumtoxinA 200 U

Reporting group description

Subject analysis set title

OnabotulinumtoxinA 50 U

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

OnabotulinumtoxinA 100 U

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

OnabotulinumtoxinA 200 U

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

OnabotulinumtoxinA 50 U

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

OnabotulinumtoxinA 100 U

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

OnabotulinumtoxinA 200 U

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

OnabotulinumtoxinA 50 U

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

OnabotulinumtoxinA 50 U (Treatment Cycle 1)

Subject analysis set type

Sub-group analysis

Subject analysis set description

OnabotulinumtoxinA (botulinum toxin Type A) 50 U (not to exceed 6 U/kg) injected into the detrusor wall on Day 1 in Treatment Cycle 1. Participants were eligible for retreatment after Week 12 if qualified. Blinded dose increases (one level) were allowed based on clinical response from cycle to cycle (not to exceed 6 U/kg).

Subject analysis set title

OnabotulinumtoxinA 100 U (Treatment Cycle 1)

Subject analysis set type

Sub-group analysis

Subject analysis set description

OnabotulinumtoxinA (botulinum toxin Type A) 100 U (not to exceed 6 U/kg) injected into the detrusor wall on Day 1 in Treatment Cycle 1. Participants were eligible for retreatment after Week 12 if qualified. Blinded dose increases (one level) were allowed based on clinical response from cycle to cycle (not to exceed 6 U/kg).

Subject analysis set title

OnabotulinumtoxinA 200 U (Treatment Cycle 1)

Subject analysis set type

Sub-group analysis

Subject analysis set description

OnabotulinumtoxinA (botulinum toxin Type A) 200 U (not to exceed 6 U/kg) injected into the detrusor wall on Day 1 in Treatment Cycle 1. Participants were eligible for retreatment after Week 12 if qualified. Blinded dose increases (one level) were allowed based on clinical response from cycle to cycle (not to exceed 6 U/kg).

Subject analysis set title

OnabotulinumtoxinA 50 U (Treatment Cycle 2)

Subject analysis set type

Sub-group analysis

Subject analysis set description

OnabotulinumtoxinA (botulinum toxin Type A) 50 U (not to exceed 6 U/kg) injected into the detrusor wall on Day 1 in Treatment Cycle 2. Participants were eligible for retreatment after Week 12 if qualified. Blinded dose increases (one level) were allowed based on clinical response from cycle to cycle (not to exceed 6 U/kg).

Subject analysis set title

OnabotulinumtoxinA 100 U (Treatment Cycle 2)

Subject analysis set type

Sub-group analysis

Subject analysis set description

OnabotulinumtoxinA (botulinum toxin Type A) 100 U (not to exceed 6 U/kg) injected into the detrusor wall on Day 1 in Treatment Cycle 2. Participants were eligible for retreatment after Week 12 if qualified. Blinded dose increases (one level) were allowed based on clinical response from cycle to cycle (not to exceed 6 U/kg).

Subject analysis set title

OnabotulinumtoxinA 200 U (Treatment Cycle 2)

Subject analysis set type

Sub-group analysis

Subject analysis set description

OnabotulinumtoxinA (botulinum toxin Type A) 200 U (not to exceed 6 U/kg) injected into the detrusor wall on Day 1 in Treatment Cycle 2. Participants were eligible for retreatment after Week 12 if qualified. Blinded dose increases (one level) were allowed based on clinical response from cycle to cycle (not to exceed 6 U/kg).

Subject analysis set title

OnabotulinumtoxinA 50 U (Treatment Cycle 3)

Subject analysis set type

Sub-group analysis

Subject analysis set description

OnabotulinumtoxinA (botulinum toxin Type A) 50 U (not to exceed 6 U/kg) injected into the detrusor wall on Day 1 in Treatment Cycle 3. Participants were eligible for retreatment after Week 12 if qualified. Blinded dose increases (one level) were allowed based on clinical response from cycle to cycle (not to exceed 6 U/kg).

Subject analysis set title

OnabotulinumtoxinA 100 U (Treatment Cycle 3)

Subject analysis set type

Sub-group analysis

Subject analysis set description

OnabotulinumtoxinA (botulinum toxin Type A) 100 U (not to exceed 6 U/kg) injected into the detrusor wall on Day 1 in Treatment Cycle 3. Participants were eligible for retreatment after Week 12 if qualified. Blinded dose increases (one level) were allowed based on clinical response from cycle to cycle (not to exceed 6 U/kg).

Subject analysis set title

OnabotulinumtoxinA 200 U (Treatment Cycle 3)

Subject analysis set type

Sub-group analysis

Subject analysis set description

OnabotulinumtoxinA (botulinum toxin Type A) 200 U (not to exceed 6 U/kg) injected into the detrusor wall on Day 1 in Treatment Cycle 3. Participants were eligible for retreatment after Week 12 if qualified. Blinded dose increases (one level) were allowed based on clinical response from cycle to cycle (not to exceed 6 U/kg).

Subject analysis set title

OnabotulinumtoxinA 50 U (Treatment Cycle 4)

Subject analysis set type

Sub-group analysis

Subject analysis set description

OnabotulinumtoxinA (botulinum toxin Type A) 50 U (not to exceed 6 U/kg) injected into the detrusor wall on Day 1 in Treatment Cycle 4. Blinded dose increases (one level) were allowed based on clinical response from cycle to cycle (not to exceed 6 U/kg).

Subject analysis set title

OnabotulinumtoxinA 100 U (Treatment Cycle 4)

Subject analysis set type

Sub-group analysis

Subject analysis set description

OnabotulinumtoxinA (botulinum toxin Type A) 100 U (not to exceed 6 U/kg) injected into the detrusor wall on Day 1 in Treatment Cycle 4. Blinded dose increases (one level) were allowed based on clinical response from cycle to cycle (not to exceed 6 U/kg).

Subject analysis set title

OnabotulinumtoxinA 200 U (Treatment Cycle 4)

Subject analysis set type

Sub-group analysis

Subject analysis set description

OnabotulinumtoxinA (botulinum toxin Type A) 200 U (not to exceed 6 U/kg) injected into the detrusor wall on Day 1 in Treatment Cycle 4. Blinded dose increases (one level) were allowed based on clinical response from cycle to cycle (not to exceed 6 U/kg).

Primary: Change From Study Baseline in the Daily Normalized Daytime Average Number of Urinary Incontinence Episodes in Treatment Cycle 1

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End point title

Change From Study Baseline in the Daily Normalized Daytime Average Number of Urinary Incontinence Episodes in Treatment Cycle 1 ^[1]

End point description

Urinary incontinence was defined as involuntary loss of urine as recorded by the participant in a bladder diary during 2 consecutive days in the week prior to the study visit (normalized to a 12 hour daytime period). Daytime is defined as the time between waking up to start the day and going to bed to sleep for the night. The number of daily daytime incontinence episodes were averaged during the 2-day period. A negative change from Baseline indicates improvement. Data are summarized under the respective treatments that participants received in the corresponding treatment cycle. BOTOX-treated Population included all participants enrolled into the extension study who received at least 1 BOTOX treatment over the course of the total evaluation period, starting from their first treatment in Study 120. 'n' is the number of participants with evaluable data at the given time point.

End point type

Primary

End point timeframe

Study Baseline (Prior to Day 1 in Study 120) to 2 consecutive days in the week prior to Week 6 in Treatment Cycle 1

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analyses were not available

End point values	OnabotulinumtoxinA 50 U (Treatment Cycle 1)	OnabotulinumtoxinA 100 U (Treatment Cycle 1)	OnabotulinumtoxinA 200 U (Treatment Cycle 1)
Number of subjects analysed	31	39	25
Units: urinary incontinence episodes per day
arithmetic mean (standard deviation)
Baseline (n= 31, 39, 25)	2.66 ± 0.876	2.97 ± 1.135	3.99 ± 5.492
Change from Baseline to Week 6 (n= 30, 36, 23)	-1.19 ± 1.156	-1.39 ± 1.585	-2.19 ± 5.738

No statistical analyses for this end point

Primary: Change From Study Baseline in the Daily Normalized Daytime Average Number of Urinary Incontinence Episodes in Treatment Cycle 2

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End point title

Change From Study Baseline in the Daily Normalized Daytime Average Number of Urinary Incontinence Episodes in Treatment Cycle 2 ^[2]

End point description

Urinary incontinence was defined as involuntary loss of urine as recorded by the participant in a bladder diary during 2 consecutive days in the week prior to the study visit (normalized to a 12 hour daytime period). Daytime is defined as the time between waking up to start the day and going to bed to sleep for the night. The number of daily daytime incontinence episodes were averaged during the 2-day period. A negative change from Baseline indicates improvement. Data are summarized under the respective treatments that participants received in the corresponding treatment cycle. BOTOX-treated Population included all participants enrolled into the extension study who received at least 1 BOTOX treatment over the course of the total evaluation period, starting from their first treatment in Study 120. 'n' is the number of participants with evaluable data at the given time point.

End point type

Primary

End point timeframe

Study Baseline (Prior to Day 1 in Study 120) to 2 consecutive days in the week prior to Week 6 in Treatment Cycle 2

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analyses were not available

End point values	OnabotulinumtoxinA 50 U (Treatment Cycle 2)	OnabotulinumtoxinA 100 U (Treatment Cycle 2)	OnabotulinumtoxinA 200 U (Treatment Cycle 2)
Number of subjects analysed	9	45	36
Units: urinary incontinence episodes per day
arithmetic mean (standard deviation)
Baseline (n=9, 45, 36)	2.57 ± 0.937	2.80 ± 0.915	3.83 ± 4.623
Change from Baseline to Week 6 (n=6, 44, 34)	-1.07 ± 2.092	-1.70 ± 1.331	-1.64 ± 1.906

No statistical analyses for this end point

Primary: Change From Study Baseline in the Daily Normalized Daytime Average Number of Urinary Incontinence Episodes in Treatment Cycle 3

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End point title

Change From Study Baseline in the Daily Normalized Daytime Average Number of Urinary Incontinence Episodes in Treatment Cycle 3 ^[3]

End point description

End point type

Primary

End point timeframe

Study Baseline (Prior to Day 1 in Study 120) to 2 consecutive days in the week prior to Week 6 in Treatment Cycle 3

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analyses were not available

End point values	OnabotulinumtoxinA 50 U (Treatment Cycle 3)	OnabotulinumtoxinA 100 U (Treatment Cycle 3)	OnabotulinumtoxinA 200 U (Treatment Cycle 3)
Number of subjects analysed	5	16	34
Units: urinary incontinence episodes per day
arithmetic mean (standard deviation)
Baseline (n=5, 16, 34)	2.48 ± 0.228	2.94 ± 0.923	3.80 ± 4.678
Change from Baseline to Week 6 (n=5, 16, 33)	-1.92 ± 0.858	-1.73 ± 1.057	-2.74 ± 4.833

No statistical analyses for this end point

Secondary: Number of Participants with Treatment Emergent Adverse Events (TEAEs) and Serious Treatment Emergent Adverse Events (STEAEs)

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End point title

Number of Participants with Treatment Emergent Adverse Events (TEAEs) and Serious Treatment Emergent Adverse Events (STEAEs)

End point description

Adverse event:any untoward medical occurrence in patient or clinical investigation participant administered pharmaceutical product,which does not necessarily have causal relationship with treatment.It can therefore be any unfavorable and unintended sign(including abnormal laboratory finding),symptom,or disease temporally associated with use of medicinal(investigational)product,whether or not related to medicinal product.Serious AE(SAE):any AE resulted in death,inpatient hospitalization/prolongation of existing hospitalization,persistent or significant disability/incapacity,life threatening,congenital anomaly/birth defect or important medical event.TEAE/STEAE:any new AE/worsening of existing condition after initiation of treatment.Data summarized under respective treatments participants received in corresponding treatment cycles.BOTOX-treated Population:all participants enrolled into Study121,received >=1BOTOX treatment during total evaluation period,from first treatment in Study120.

End point type

Secondary

End point timeframe

First injection on Day 1 in Study 120 through completion of Study 121 (Up to 108 weeks)

End point values	OnabotulinumtoxinA 50 U (Treatment Cycle 1)	OnabotulinumtoxinA 100 U (Treatment Cycle 1)	OnabotulinumtoxinA 200 U (Treatment Cycle 1)	OnabotulinumtoxinA 50 U (Treatment Cycle 2)	OnabotulinumtoxinA 100 U (Treatment Cycle 2)	OnabotulinumtoxinA 200 U (Treatment Cycle 2)	OnabotulinumtoxinA 50 U (Treatment Cycle 3)	OnabotulinumtoxinA 100 U (Treatment Cycle 3)	OnabotulinumtoxinA 200 U (Treatment Cycle 3)	OnabotulinumtoxinA 50 U (Treatment Cycle 4)	OnabotulinumtoxinA 100 U (Treatment Cycle 4)	OnabotulinumtoxinA 200 U (Treatment Cycle 4)
Number of subjects analysed	31	39	25	9	45	36	5	16	34	3	4	4
Units: participants
TEAEs	23	31	19	7	34	31	4	10	21	3	2	4
STEAEs	2	3	1	0	5	6	0	1	2	0	0	0

No statistical analyses for this end point

Secondary: Percentage of Participants with ≥ 50%, ≥ 75%, ≥ 90%, and ≥ 100% Reduction from Baseline in the Number of Normalized Daytime Urinary Incontinence Episodes in Treatment Cycle 1

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End point title

Percentage of Participants with ≥ 50%, ≥ 75%, ≥ 90%, and ≥ 100% Reduction from Baseline in the Number of Normalized Daytime Urinary Incontinence Episodes in Treatment Cycle 1

End point description

Urinary incontinence was defined as involuntary loss of urine as recorded by the participant in a bladder diary during 2 consecutive days in the week prior to the study visit (normalized to a 12 hour daytime period). Daytime is defined as the time between waking up to start the day and going to bed to sleep for the night. The number of daily incontinence episodes were averaged during the 2-day period. Data are summarized under the respective treatments that participants received in the corresponding treatment cycle. BOTOX-treated Population included all participants enrolled into extension study who received at least 1 BOTOX treatment over the course of total evaluation period, starting from their first treatment in Study 120. Number analysed is the number of participants with evaluable data for the specific category.

End point type

Secondary

End point timeframe

Study Baseline (Prior to Day 1 in Study 120) to 2 consecutive days in the week prior to Week 6 in Treatment Cycle 1

End point values	OnabotulinumtoxinA 50 U (Treatment Cycle 1)	OnabotulinumtoxinA 100 U (Treatment Cycle 1)	OnabotulinumtoxinA 200 U (Treatment Cycle 1)
Number of subjects analysed	30	36	23
Units: percentage of participants
number (confidence interval 95%)
≥50% Reduction from Baseline to Week 6	53.3 (34.33 to 71.66)	55.6 (38.10 to 72.06)	52.2 (30.59 to 73.18)
≥75% Reduction from Baseline to Week 6	30.0 (14.73 to 49.40)	41.7 (25.51 to 59.24)	39.1 (19.71 to 61.46)
≥90% Reduction from Baseline to Week 6	26.7 (12.28 to 45.89)	30.6 (16.35 to 48.11)	30.4 (13.21 to 52.92)
≥100% Reduction from Baseline to Week 6	26.7 (12.28 to 45.89)	27.8 (14.20 to 45.19)	26.1 (10.23 to 48.41)

No statistical analyses for this end point

Secondary: Percentage of Participants with ≥ 50%, ≥ 75%, ≥ 90%, and ≥ 100% Reduction from Baseline in the Number of Normalized Daytime Urinary Incontinence Episodes in Treatment Cycle 2

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End point title

Percentage of Participants with ≥ 50%, ≥ 75%, ≥ 90%, and ≥ 100% Reduction from Baseline in the Number of Normalized Daytime Urinary Incontinence Episodes in Treatment Cycle 2

End point description

Urinary incontinence was defined as involuntary loss of urine as recorded by the participant in a bladder diary during 2 consecutive days in the week prior to the study visit (normalized to a 12 hour daytime period). Daytime is defined as the time between waking up to start the day and going to bed to sleep for the night. The number of daily incontinence episodes were averaged during the 2-day period. Data are summarized under the respective treatments that participants received in the corresponding treatment cycle. BOTOX-treated Population included all participants enrolled into extension study who received at least 1 BOTOX treatment over the course of total evaluation period, starting from their first treatment in Study 120. Number analysed is the number of participants with evaluable data for the specific category.

End point type

Secondary

End point timeframe

Study Baseline (Prior to Day 1 in Study 120) to 2 consecutive days in the week prior to Week 6 in Treatment Cycle 2

End point values	OnabotulinumtoxinA 50 U (Treatment Cycle 2)	OnabotulinumtoxinA 100 U (Treatment Cycle 2)	OnabotulinumtoxinA 200 U (Treatment Cycle 2)
Number of subjects analysed	6	44	34
Units: percentage of participants
number (confidence interval 95%)
≥50% Reduction from Baseline to Week 6	66.7 (22.28 to 95.67)	65.9 (50.08 to 79.51)	58.8 (40.70 to 75.35)
≥75% Reduction from Baseline to Week 6	50.0 (11.81 to 88.19)	43.2 (28.35 to 58.97)	47.1 (29.78 to 64.87)
≥90% Reduction from Baseline to Week 6	50.0 (11.81 to 88.19)	27.3 (14.96 to 42.79)	41.2 (24.65 to 59.30)
≥100% Reduction from Baseline to Week 6	50.0 (11.81 to 88.19)	25.0 (13.19 to 40.34)	38.2 (22.17 to 56.44)

No statistical analyses for this end point

Secondary: Percentage of Participants with ≥ 50%, ≥ 75%, ≥ 90%, and ≥ 100% Reduction from Baseline in the Number of Normalized Daytime Urinary Incontinence Episodes in Treatment Cycle 3

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End point title

Percentage of Participants with ≥ 50%, ≥ 75%, ≥ 90%, and ≥ 100% Reduction from Baseline in the Number of Normalized Daytime Urinary Incontinence Episodes in Treatment Cycle 3

End point description

Urinary incontinence was defined as involuntary loss of urine as recorded by the participant in a bladder diary during 2 consecutive days in the week prior to the study visit (normalized to a 12 hour daytime period). Daytime is defined as the time between waking up to start the day and going to bed to sleep for the night. The number of daily incontinence episodes were averaged during the 2-day period.  Data are summarized under the respective treatments that participants received in the corresponding treatment cycle. BOTOX-treated Population included all participants enrolled into extension study who received at least 1 BOTOX treatment over the course of total evaluation period, starting from their first treatment in Study 120. Number analysed is the number of participants with evaluable data for the specific category.

End point type

Secondary

End point timeframe

Study Baseline (Prior to Day 1 in Study 120) to 2 consecutive days in the week prior to Week 6 in Treatment Cycle 3

End point values	OnabotulinumtoxinA 50 U (Treatment Cycle 3)	OnabotulinumtoxinA 100 U (Treatment Cycle 3)	OnabotulinumtoxinA 200 U (Treatment Cycle 3)
Number of subjects analysed	5	16	33
Units: percentage of participants
number (confidence interval 95%)
≥50% Reduction from Baseline at Week 6	60.0 (14.66 to 94.73)	75.0 (47.62 to 92.73)	69.7 (51.29 to 84.41)
≥75% Reduction from Baseline at Week 6	60.0 (14.66 to 94.73)	37.5 (15.20 to 64.57)	39.4 (22.91 to 57.86)
≥90% Reduction from Baseline at Week 6	60.0 (14.66 to 94.73)	18.8 (4.05 to 45.65)	33.3 (17.96 to 51.83)
≥100% Reduction from Baseline at Week 6	60.0 (14.66 to 94.73)	18.8 (4.05 to 45.65)	30.3 (15.59 to 48.71)

No statistical analyses for this end point

Secondary: Change from Baseline in Average Urine Volume at First Morning Catheterization in Treatment Cycle 1

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End point title

Change from Baseline in Average Urine Volume at First Morning Catheterization in Treatment Cycle 1

End point description

The change in urine volume at first morning catherization was recorded by the participant in a bladder diary in the 2 consecutive days during the week prior to the study visit. The daily values were averaged during the 2-day period. A positive change from Baseline indicates improvement. Data are summarized under the respective treatments that participants received in the corresponding treatment cycle. BOTOX-treated Population included all participants enrolled into extension study who received >=1 BOTOX treatment over course of total evaluation period, starting from their first treatment in Study 120. Overall number of participants analysed is the number of participants with data available for analyses.

End point type

Secondary

End point timeframe

Baseline (Prior to Day 1 in Study 120) to 2 consecutive days in the week prior to Week 6 in Treatment Cycle 1

End point values	OnabotulinumtoxinA 50 U (Treatment Cycle 1)	OnabotulinumtoxinA 100 U (Treatment Cycle 1)	OnabotulinumtoxinA 200 U (Treatment Cycle 1)
Number of subjects analysed	30	36	21
Units: mL
arithmetic mean (standard deviation)	14.68 ± 88.146	39.88 ± 72.787	96.90 ± 120.429

No statistical analyses for this end point

Secondary: Change from Baseline in Average Urine Volume at First Morning Catheterization in Treatment Cycle 2

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End point title

Change from Baseline in Average Urine Volume at First Morning Catheterization in Treatment Cycle 2

End point description

End point type

Secondary

End point timeframe

Baseline (Prior to Day 1 in Study 120) to 2 consecutive days in the week prior to Week 6 in Treatment Cycle 2

End point values	OnabotulinumtoxinA 50 U (Treatment Cycle 2)	OnabotulinumtoxinA 100 U (Treatment Cycle 2)	OnabotulinumtoxinA 200 U (Treatment Cycle 2)
Number of subjects analysed	6	43	31
Units: mL
arithmetic mean (standard deviation)	7.92 ± 148.597	79.53 ± 106.794	35.34 ± 98.209

No statistical analyses for this end point

Secondary: Change from Baseline in Average Urine Volume at First Morning Catheterization in Treatment Cycle 3

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End point title

Change from Baseline in Average Urine Volume at First Morning Catheterization in Treatment Cycle 3

End point description

End point type

Secondary

End point timeframe

Baseline (Prior to Day 1 in Study 120) to 2 consecutive days in the week prior to Week 6 in Treatment Cycle 3

End point values	OnabotulinumtoxinA 50 U (Treatment Cycle 3)	OnabotulinumtoxinA 100 U (Treatment Cycle 3)	OnabotulinumtoxinA 200 U (Treatment Cycle 3)
Number of subjects analysed	5	10	31
Units: mL
arithmetic mean (standard deviation)	58.50 ± 22.749	57.86 ± 74.762	92.39 ± 147.322

No statistical analyses for this end point

Secondary: Percentage of Participants with Night Time Urinary Incontinence in Treatment Cycle 1

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End point title

Percentage of Participants with Night Time Urinary Incontinence in Treatment Cycle 1

End point description

Urinary incontinence was defined as involuntary loss of urine. Night time urinary incontinence was recorded by the participant on the bladder diary as a presence or absence of urinary leakage upon waking, for 2 consecutive days in the week prior to the week 6 visit. Night time was defined as the time between going to bed to sleep for the night and waking up to start the day. The percentage of participants with night time urinary incontinence is presented in categories 0, 1, and 2 nights. Data are summarized under the respective treatments that participants received in the corresponding treatment cycle. BOTOX-treated Population included all participants enrolled into extension study who received >= 1 BOTOX treatment over course of total evaluation period, starting from their first treatment in Study 120. 'n' is the number of participants with data available for analyses at the given time point.

End point type

Secondary

End point timeframe

Baseline (Prior to Day 1 in Study 120) and 2 consecutive days in the week prior to Week 6 in Treatment Cycle 1

End point values	OnabotulinumtoxinA 50 U (Treatment Cycle 1)	OnabotulinumtoxinA 100 U (Treatment Cycle 1)	OnabotulinumtoxinA 200 U (Treatment Cycle 1)
Number of subjects analysed	31	39	25
Units: percentage of participants
number (not applicable)
0 Nights of Incontinence at Baseline (n=31,39,23)	0.0	15.4	4.3
0 Nights of Incontinence at Week 6 (n=30,37,24)	30.0	37.8	25.0
1 Night of Incontinence at Baseline (n=31,39,23)	12.9	2.6	17.4
1 Night of Incontinence at Week 6 (n=30,37,24)	20.0	16.2	29.2
2 Nights of Incontinence at Baseline (n=31,39,23)	87.1	82.1	78.3
2 Nights of Incontinence at Week 6 (n=30,37,24)	50.0	45.9	45.8

No statistical analyses for this end point

Secondary: Percentage of Participants with Night Time Urinary Incontinence in Treatment Cycle 2

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End point title

Percentage of Participants with Night Time Urinary Incontinence in Treatment Cycle 2

End point description

End point type

Secondary

End point timeframe

Baseline (Prior to Day 1 in Study 120) and 2 consecutive days in the week prior to Week 6 in Treatment Cycle 2

End point values	OnabotulinumtoxinA 50 U (Treatment Cycle 2)	OnabotulinumtoxinA 100 U (Treatment Cycle 2)	OnabotulinumtoxinA 200 U (Treatment Cycle 2)
Number of subjects analysed	9	45	36
Units: percentage of participants
number (not applicable)
0 Nights of Incontinence at Baseline (n=9, 45, 34)	0.0	8.9	5.9
0 Nights of Incontinence at Week 6 (n=6, 44, 34)	66.7	34.1	23.5
1 Night of Incontinence at Baseline (n=9, 45, 34)	22.2	6.7	8.8
1 Night of Incontinence at Week 6 (n=6, 44, 34)	16.7	22.7	8.8
2 Nights of Incontinence at Baseline (n=9, 45, 34)	77.8	84.4	85.3
2 Nights of Incontinence at Week 6 (n=6, 44, 34)	16.7	43.2	67.6

No statistical analyses for this end point

Secondary: Percentage of Participants with Night Time Urinary Incontinence in Treatment Cycle 3

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End point title

Percentage of Participants with Night Time Urinary Incontinence in Treatment Cycle 3

End point description

End point type

Secondary

End point timeframe

Baseline (Prior to Day 1 in Study 120) and 2 consecutive days in the week prior to Week 6 in Treatment Cycle 3

End point values	OnabotulinumtoxinA 50 U (Treatment Cycle 3)	OnabotulinumtoxinA 100 U (Treatment Cycle 3)	OnabotulinumtoxinA 200 U (Treatment Cycle 3)
Number of subjects analysed	5	16	34
Units: percentage of participants
number (not applicable)
0 Nights of Incontinence at Baseline (n=5, 16, 34)	0.0	12.5	5.9
0 Nights of Incontinence at Week 6 (n=5, 16, 33)	20.0	31.3	21.2
1 Night of Incontinence at Baseline (n=5, 16, 34)	0.0	0.0	5.9
1 Night of Incontinence at Week 6 (n=5, 16, 33)	40.0	12.5	27.3
2 Nights of Incontinence at Baseline (n=5, 16, 34)	100.0	87.5	88.2
2 Nights of Incontinence at Week 6 (n=5, 16, 33)	40.0	56.3	51.5

No statistical analyses for this end point

Secondary: Average Time to Participant's Request for Retreatment

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End point title

Average Time to Participant's Request for Retreatment

End point description

Time to request for re-treatment is the time in weeks between last injection and request for next injection, regardless of fulfillment of the re-treatment criteria. Data are summarized under the respective treatments that participants received across entire study. Data is reported for only participants that had at least one request for retreatment while on a specified BOTOX dose. BOTOX-treated Population included all participants enrolled into extension study who received >=1 BOTOX treatment over course of total evaluation period, starting from their first treatment in Study 120. Overall number of participants analysed is the number of participants with data available for analyses.

End point type

Secondary

End point timeframe

First injection on Day 1 in Study 120 through to the date of completion of Study 121 (Up to 108 weeks)

End point values	OnabotulinumtoxinA 50 U	OnabotulinumtoxinA 100 U	OnabotulinumtoxinA 200 U
Number of subjects analysed	30	53	35
Units: weeks
median (full range (min-max))	24.55 (11.9 to 89.7)	24.64 (11.7 to 73.3)	25.43 (11.1 to 78.9)

No statistical analyses for this end point

Secondary: Average Time to Participant's Qualification for Retreatment

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End point title

Average Time to Participant's Qualification for Retreatment

End point description

The criteria for qualification of retreatment included 1) Participant/parent/caregiver requests retreatment; 2) Participant has a total of at least 2 daytime urinary incontinence episodes over the 2-day bladder diary collection period; 3) At least 12 weeks has elapsed since treatment 1 and 4) Participant has not experienced a serious treatment-related adverse event at any time. Data are summarized under the respective treatments that participants received across entire study. Data is reported for only participants that had at least one request for retreatment while on a specified BOTOX dose. BOTOX-treated Population included all participants enrolled into extension study who received >=1 BOTOX treatment over course of total evaluation period, starting from their first treatment in Study 120. Overall number of participants analysed is the number of participants with data available for analyses.

End point type

Secondary

End point timeframe

First injection on Day 1 in Study 120 through to the date of completion of Study 121 (Up to 108 weeks)

End point values	OnabotulinumtoxinA 200 U	OnabotulinumtoxinA 100 U	OnabotulinumtoxinA 50 U
Number of subjects analysed	25	53	29
Units: weeks
median (confidence interval 95%)	26.29 (11.1 to 78.9)	25.43 (11.7 to 76.1)	25.38 (11.9 to 84.4)

No statistical analyses for this end point

Secondary: Percentage of Participants with Positive Response on Modified Treatment Benefit Scale (TBS) in Treatment Cycle 1

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End point title

Percentage of Participants with Positive Response on Modified Treatment Benefit Scale (TBS) in Treatment Cycle 1

End point description

The Modified TBS is a single-item scale which assesses the participant’s condition (urinary problems, urinary incontinence) on a 4-point scale where 1 = greatly improved; 2 = improved; 3 = not changed; and 4 = worsened. A participant was considered to have a positive treatment response if they responded to the TBS question as either “greatly improved” or “improved”. Data are summarized under the respective treatments that participants received in the corresponding treatment cycle. BOTOX-treated Population included all participants enrolled into extension study who received >=1 BOTOX treatment over course of total evaluation period,starting from their first treatment in Study 120. Overall number of participants analysed is number of participants with data available for analyses.

End point type

Secondary

End point timeframe

Week 6 in Treatment Cycle 1

End point values	OnabotulinumtoxinA 50 U (Treatment Cycle 1)	OnabotulinumtoxinA 100 U (Treatment Cycle 1)	OnabotulinumtoxinA 200 U (Treatment Cycle 1)
Number of subjects analysed	30	35	24
Units: percentage of participants
number (confidence interval 95%)	80.0 (61.43 to 92.29)	80.0 (63.06 to 91.56)	75.0 (53.29 to 90.23)

No statistical analyses for this end point

Secondary: Percentage of Participants with Positive Response on Modified Treatment Benefit Scale (TBS) in Treatment Cycle 2

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End point title

Percentage of Participants with Positive Response on Modified Treatment Benefit Scale (TBS) in Treatment Cycle 2

End point description

The Modified TBS is a single-item scale which assesses the participant’s condition (urinary problems, urinary incontinence) on a 4-point scale where 1 = greatly improved; 2 = improved; 3 = not changed; and 4 = worsened. A participant was considered to have a positive treatment response if they responded to the TBS question as either “greatly improved” or “improved”. Data are summarized under the respective treatments that participants received in the corresponding treatment cycle. BOTOX-treated Population included all participants enrolled into extension study who received >=1 BOTOX treatment over course of total evaluation period,starting from their first treatment in Study 120. Overall number of participants analysed is the number of participants with data available for analyses.

End point type

Secondary

End point timeframe

Week 6 in Treatment Cycle 2

End point values	OnabotulinumtoxinA 50 U (Treatment Cycle 2)	OnabotulinumtoxinA 100 U (Treatment Cycle 2)	OnabotulinumtoxinA 200 U (Treatment Cycle 2)
Number of subjects analysed	8	42	30
Units: percentage of participants
number (confidence interval 95%)	75.0 (34.91 to 96.81)	97.6 (87.43 to 99.94)	83.3 (65.28 to 94.36)

No statistical analyses for this end point

Secondary: Percentage of Participants with Positive Response on Modified Treatment Benefit Scale (TBS) in Treatment Cycle 3

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End point title

Percentage of Participants with Positive Response on Modified Treatment Benefit Scale (TBS) in Treatment Cycle 3

End point description

The Modified TBS is a single-item scale which assesses the participant’s condition (urinary problems, urinary incontinence) on a 4-point scale where 1 = greatly improved; 2 = improved; 3 = not changed; and 4 = worsened. A participant was considered to have a positive treatment response if they responded to the TBS question as either “greatly improved” or “improved”. Data are summarized under the respective treatments that participants received in the corresponding treatment cycle. BOTOX-treated Population included all participants enrolled into extension study who received >=1 BOTOX treatment over course of total evaluation period,starting from their first treatment in Study 120. Overall number of participants analysed is the number of participants with data available for analyses.

End point type

Secondary

End point timeframe

Week 6 in Treatment Cycle 3

End point values	OnabotulinumtoxinA 50 U (Treatment Cycle 3)	OnabotulinumtoxinA 100 U (Treatment Cycle 3)	OnabotulinumtoxinA 200 U (Treatment Cycle 3)
Number of subjects analysed	5	15	33
Units: percentage of participants
number (confidence interval 95%)	100 (47.82 to 100.00)	80.0 (51.91 to 95.67)	84.8 (68.10 to 94.89)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

First injection on Day 1 in Study 120 through the completion of Study 121 (Up to 108 Weeks)

Adverse event reporting additional description

BOTOX-treated Population included all participants enrolled into the extension study who received at least 1 BOTOX treatment over the course of the total evaluation period, starting from their first treatment in Study 191622-120. Data are summarized under the respective treatments that participants received in the corresponding treatment cycles.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

19.0

Reporting group title

OnabotulinumtoxinA 100 U (Treatment Cycle 1)

Reporting group description

Reporting group title

OnabotulinumtoxinA 50 U (Treatment Cycle 1)

Reporting group description

Reporting group title

OnabotulinumtoxinA 200 U (Treatment Cycle 1)

Reporting group description

Reporting group title

OnabotulinumtoxinA 50 U (Treatment Cycle 2)

Reporting group description

Reporting group title

OnabotulinumtoxinA 100 U (Treatment Cycle 2)

Reporting group description

Reporting group title

OnabotulinumtoxinA 200 U (Treatment Cycle 2)

Reporting group description

Reporting group title

OnabotulinumtoxinA 50 U (Treatment Cycle 3)

Reporting group description

Reporting group title

OnabotulinumtoxinA 100 U (Treatment Cycle 3)

Reporting group description

Reporting group title

OnabotulinumtoxinA 200 U (Treatment Cycle 3)

Reporting group description

Reporting group title

OnabotulinumtoxinA 50 U (Treatment Cycle 4)

Reporting group description

Reporting group title

OnabotulinumtoxinA 100 U (Treatment Cycle 4)

Reporting group description

Reporting group title

OnabotulinumtoxinA 200 U (Treatment Cycle 4)

Reporting group description

OnabotulinumtoxinA 100 U (Treatment Cycle 1)

OnabotulinumtoxinA 50 U (Treatment Cycle 1)

OnabotulinumtoxinA 200 U (Treatment Cycle 1)

OnabotulinumtoxinA 50 U (Treatment Cycle 2)

OnabotulinumtoxinA 100 U (Treatment Cycle 2)

OnabotulinumtoxinA 200 U (Treatment Cycle 2)

OnabotulinumtoxinA 50 U (Treatment Cycle 3)

OnabotulinumtoxinA 100 U (Treatment Cycle 3)

OnabotulinumtoxinA 200 U (Treatment Cycle 3)

OnabotulinumtoxinA 50 U (Treatment Cycle 4)

OnabotulinumtoxinA 100 U (Treatment Cycle 4)

OnabotulinumtoxinA 200 U (Treatment Cycle 4)

Total subjects affected by serious adverse events

subjects affected / exposed

3 / 39 (7.69%)

2 / 31 (6.45%)

1 / 25 (4.00%)

0 / 9 (0.00%)

5 / 45 (11.11%)

6 / 36 (16.67%)

0 / 5 (0.00%)

1 / 16 (6.25%)

2 / 34 (5.88%)

0 / 3 (0.00%)

0 / 4 (0.00%)

number of deaths (all causes)

number of deaths resulting from adverse events

Injury, poisoning and procedural complications

Arteriovenous fistula thrombosis

subjects affected / exposed

0 / 39 (0.00%)

1 / 31 (3.23%)

0 / 25 (0.00%)

0 / 9 (0.00%)

0 / 45 (0.00%)

0 / 36 (0.00%)

0 / 5 (0.00%)

0 / 16 (0.00%)

0 / 34 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Joint dislocation

subjects affected / exposed

0 / 39 (0.00%)

0 / 31 (0.00%)

0 / 25 (0.00%)

0 / 9 (0.00%)

1 / 45 (2.22%)

0 / 36 (0.00%)

0 / 5 (0.00%)

0 / 16 (0.00%)

0 / 34 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular disorders

Hypertension

subjects affected / exposed

0 / 39 (0.00%)

0 / 31 (0.00%)

1 / 25 (4.00%)

0 / 9 (0.00%)

0 / 45 (0.00%)

0 / 36 (0.00%)

0 / 5 (0.00%)

0 / 16 (0.00%)

0 / 34 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nervous system disorders

Hydrocephalus

subjects affected / exposed

1 / 39 (2.56%)

0 / 31 (0.00%)

0 / 25 (0.00%)

0 / 9 (0.00%)

0 / 45 (0.00%)

0 / 36 (0.00%)

0 / 5 (0.00%)

0 / 16 (0.00%)

0 / 34 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Epilepsy

subjects affected / exposed

0 / 39 (0.00%)

0 / 31 (0.00%)

0 / 25 (0.00%)

0 / 9 (0.00%)

0 / 45 (0.00%)

0 / 36 (0.00%)

0 / 5 (0.00%)

1 / 16 (6.25%)

0 / 34 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Skin and subcutaneous tissue disorders

Psoriasis

subjects affected / exposed

0 / 39 (0.00%)

0 / 31 (0.00%)

0 / 25 (0.00%)

0 / 9 (0.00%)

0 / 45 (0.00%)

1 / 36 (2.78%)

0 / 5 (0.00%)

0 / 16 (0.00%)

0 / 34 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal and urinary disorders

Hydronephrosis

subjects affected / exposed

0 / 39 (0.00%)

0 / 31 (0.00%)

0 / 25 (0.00%)

0 / 9 (0.00%)

1 / 45 (2.22%)

0 / 36 (0.00%)

0 / 5 (0.00%)

0 / 16 (0.00%)

0 / 34 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

Fistula

subjects affected / exposed

0 / 39 (0.00%)

0 / 31 (0.00%)

0 / 25 (0.00%)

0 / 9 (0.00%)

1 / 45 (2.22%)

0 / 36 (0.00%)

0 / 5 (0.00%)

0 / 16 (0.00%)

0 / 34 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hip deformity

subjects affected / exposed

0 / 39 (0.00%)

0 / 31 (0.00%)

0 / 25 (0.00%)

0 / 9 (0.00%)

1 / 45 (2.22%)

0 / 36 (0.00%)

0 / 5 (0.00%)

0 / 16 (0.00%)

0 / 34 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Foot deformity

subjects affected / exposed

0 / 39 (0.00%)

0 / 31 (0.00%)

0 / 25 (0.00%)

0 / 9 (0.00%)

0 / 45 (0.00%)

1 / 36 (2.78%)

0 / 5 (0.00%)

0 / 16 (0.00%)

0 / 34 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

Urinary tract infection

subjects affected / exposed

2 / 39 (5.13%)

1 / 31 (3.23%)

0 / 25 (0.00%)

0 / 9 (0.00%)

1 / 45 (2.22%)

2 / 36 (5.56%)

0 / 5 (0.00%)

0 / 16 (0.00%)

2 / 34 (5.88%)

0 / 3 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

1 / 2

0 / 1

0 / 0

0 / 1

0 / 2

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Encephalitis viral

subjects affected / exposed

1 / 39 (2.56%)

0 / 31 (0.00%)

0 / 25 (0.00%)

0 / 9 (0.00%)

0 / 45 (0.00%)

0 / 36 (0.00%)

0 / 5 (0.00%)

0 / 16 (0.00%)

0 / 34 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pyelonephritis

subjects affected / exposed

0 / 39 (0.00%)

0 / 31 (0.00%)

0 / 25 (0.00%)

0 / 9 (0.00%)

2 / 45 (4.44%)

0 / 36 (0.00%)

0 / 5 (0.00%)

0 / 16 (0.00%)

0 / 34 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Bacterial diarrhoea

subjects affected / exposed

0 / 39 (0.00%)

0 / 31 (0.00%)

0 / 25 (0.00%)

0 / 9 (0.00%)

1 / 45 (2.22%)

0 / 36 (0.00%)

0 / 5 (0.00%)

0 / 16 (0.00%)

0 / 34 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastroenteritis

subjects affected / exposed

0 / 39 (0.00%)

0 / 31 (0.00%)

0 / 25 (0.00%)

0 / 9 (0.00%)

1 / 45 (2.22%)

0 / 36 (0.00%)

0 / 5 (0.00%)

0 / 16 (0.00%)

0 / 34 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Bronchitis

subjects affected / exposed

0 / 39 (0.00%)

0 / 31 (0.00%)

0 / 25 (0.00%)

0 / 9 (0.00%)

0 / 45 (0.00%)

1 / 36 (2.78%)

0 / 5 (0.00%)

0 / 16 (0.00%)

0 / 34 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Febrile infection

subjects affected / exposed

0 / 39 (0.00%)

0 / 31 (0.00%)

0 / 25 (0.00%)

0 / 9 (0.00%)

0 / 45 (0.00%)

1 / 36 (2.78%)

0 / 5 (0.00%)

0 / 16 (0.00%)

0 / 34 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia

subjects affected / exposed

0 / 39 (0.00%)

0 / 31 (0.00%)

0 / 25 (0.00%)

0 / 9 (0.00%)

0 / 45 (0.00%)

1 / 36 (2.78%)

0 / 5 (0.00%)

0 / 16 (0.00%)

0 / 34 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Wound infection

subjects affected / exposed

0 / 39 (0.00%)

0 / 31 (0.00%)

0 / 25 (0.00%)

0 / 9 (0.00%)

0 / 45 (0.00%)

1 / 36 (2.78%)

0 / 5 (0.00%)

0 / 16 (0.00%)

0 / 34 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Product issues

Device malfunction

subjects affected / exposed

0 / 39 (0.00%)

0 / 31 (0.00%)

0 / 25 (0.00%)

0 / 9 (0.00%)

0 / 45 (0.00%)

1 / 36 (2.78%)

0 / 5 (0.00%)

0 / 16 (0.00%)

0 / 34 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	OnabotulinumtoxinA 100 U (Treatment Cycle 1)	OnabotulinumtoxinA 50 U (Treatment Cycle 1)	OnabotulinumtoxinA 200 U (Treatment Cycle 1)	OnabotulinumtoxinA 50 U (Treatment Cycle 2)	OnabotulinumtoxinA 100 U (Treatment Cycle 2)	OnabotulinumtoxinA 200 U (Treatment Cycle 2)	OnabotulinumtoxinA 50 U (Treatment Cycle 3)	OnabotulinumtoxinA 100 U (Treatment Cycle 3)	OnabotulinumtoxinA 200 U (Treatment Cycle 3)	OnabotulinumtoxinA 50 U (Treatment Cycle 4)	OnabotulinumtoxinA 100 U (Treatment Cycle 4)	OnabotulinumtoxinA 200 U (Treatment Cycle 4)
Total subjects affected by non serious adverse events
subjects affected / exposed	31 / 39 (79.49%)	21 / 31 (67.74%)	16 / 25 (64.00%)	7 / 9 (77.78%)	32 / 45 (71.11%)	27 / 36 (75.00%)	4 / 5 (80.00%)	10 / 16 (62.50%)	19 / 34 (55.88%)	3 / 3 (100.00%)	2 / 4 (50.00%)	4 / 4 (100.00%)
Investigations
Blood urine present
subjects affected / exposed	2 / 39 (5.13%)	0 / 31 (0.00%)	0 / 25 (0.00%)	2 / 9 (22.22%)	4 / 45 (8.89%)	2 / 36 (5.56%)	2 / 5 (40.00%)	1 / 16 (6.25%)	5 / 34 (14.71%)	2 / 3 (66.67%)	2 / 4 (50.00%)	2 / 4 (50.00%)
occurrences all number	2	0	0	2	4	2	2	1	5	2	2	2
Protein urine present
subjects affected / exposed	0 / 39 (0.00%)	0 / 31 (0.00%)	0 / 25 (0.00%)	0 / 9 (0.00%)	0 / 45 (0.00%)	2 / 36 (5.56%)	0 / 5 (0.00%)	0 / 16 (0.00%)	0 / 34 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0	0	0	0
Injury, poisoning and procedural complications
Procedural pain
subjects affected / exposed	0 / 39 (0.00%)	0 / 31 (0.00%)	0 / 25 (0.00%)	0 / 9 (0.00%)	0 / 45 (0.00%)	2 / 36 (5.56%)	0 / 5 (0.00%)	0 / 16 (0.00%)	0 / 34 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0	0	0	0
Eschar
subjects affected / exposed	0 / 39 (0.00%)	0 / 31 (0.00%)	0 / 25 (0.00%)	1 / 9 (11.11%)	0 / 45 (0.00%)	0 / 36 (0.00%)	0 / 5 (0.00%)	0 / 16 (0.00%)	0 / 34 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0
Foot fracture
subjects affected / exposed	0 / 39 (0.00%)	1 / 31 (3.23%)	0 / 25 (0.00%)	0 / 9 (0.00%)	0 / 45 (0.00%)	0 / 36 (0.00%)	0 / 5 (0.00%)	1 / 16 (6.25%)	0 / 34 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	2	0	0	0	0	0	1	0	0	0	0
Skin laceration
subjects affected / exposed	0 / 39 (0.00%)	0 / 31 (0.00%)	0 / 25 (0.00%)	0 / 9 (0.00%)	1 / 45 (2.22%)	0 / 36 (0.00%)	0 / 5 (0.00%)	1 / 16 (6.25%)	0 / 34 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	0	1	0	0	0	0
Nervous system disorders
Headache
subjects affected / exposed	7 / 39 (17.95%)	2 / 31 (6.45%)	2 / 25 (8.00%)	1 / 9 (11.11%)	3 / 45 (6.67%)	2 / 36 (5.56%)	2 / 5 (40.00%)	0 / 16 (0.00%)	1 / 34 (2.94%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	15	2	4	1	3	2	2	0	1	0	0	0
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	5 / 39 (12.82%)	1 / 31 (3.23%)	0 / 25 (0.00%)	0 / 9 (0.00%)	6 / 45 (13.33%)	3 / 36 (8.33%)	0 / 5 (0.00%)	0 / 16 (0.00%)	3 / 34 (8.82%)	0 / 3 (0.00%)	1 / 4 (25.00%)	1 / 4 (25.00%)
occurrences all number	7	1	0	0	9	3	0	0	3	0	1	1
Suprapubic pain
subjects affected / exposed	0 / 39 (0.00%)	2 / 31 (6.45%)	1 / 25 (4.00%)	0 / 9 (0.00%)	0 / 45 (0.00%)	0 / 36 (0.00%)	0 / 5 (0.00%)	0 / 16 (0.00%)	0 / 34 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	2	1	0	0	0	0	0	0	0	0	0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	2 / 39 (5.13%)	2 / 31 (6.45%)	2 / 25 (8.00%)	1 / 9 (11.11%)	2 / 45 (4.44%)	3 / 36 (8.33%)	1 / 5 (20.00%)	0 / 16 (0.00%)	0 / 34 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	8	3	2	1	2	3	1	0	0	0	0	0
Abdominal pain
subjects affected / exposed	1 / 39 (2.56%)	2 / 31 (6.45%)	1 / 25 (4.00%)	1 / 9 (11.11%)	3 / 45 (6.67%)	1 / 36 (2.78%)	0 / 5 (0.00%)	0 / 16 (0.00%)	1 / 34 (2.94%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	2	2	1	3	1	0	0	1	0	0	0
Nausea
subjects affected / exposed	0 / 39 (0.00%)	2 / 31 (6.45%)	0 / 25 (0.00%)	0 / 9 (0.00%)	1 / 45 (2.22%)	0 / 36 (0.00%)	0 / 5 (0.00%)	0 / 16 (0.00%)	1 / 34 (2.94%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	2	0	0	1	0	0	0	1	0	0	0
Vomiting
subjects affected / exposed	2 / 39 (5.13%)	0 / 31 (0.00%)	0 / 25 (0.00%)	2 / 9 (22.22%)	2 / 45 (4.44%)	0 / 36 (0.00%)	0 / 5 (0.00%)	0 / 16 (0.00%)	1 / 34 (2.94%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	2	0	0	2	4	0	0	0	1	0	0	0
Constipation
subjects affected / exposed	0 / 39 (0.00%)	0 / 31 (0.00%)	0 / 25 (0.00%)	0 / 9 (0.00%)	3 / 45 (6.67%)	0 / 36 (0.00%)	0 / 5 (0.00%)	1 / 16 (6.25%)	0 / 34 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	3	0	0	1	0	0	0	0
Reproductive system and breast disorders
Testicular retraction
subjects affected / exposed	0 / 39 (0.00%)	0 / 31 (0.00%)	0 / 25 (0.00%)	0 / 9 (0.00%)	0 / 45 (0.00%)	0 / 36 (0.00%)	0 / 5 (0.00%)	0 / 16 (0.00%)	0 / 34 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1
Dysmenorrhoea
Additional description: Number of participants at risk in the OnabotulinumtoxinA 200 U (Treatment Cycle 2) arm group is based on the female population.
subjects affected / exposed ^[1]	0 / 39 (0.00%)	0 / 31 (0.00%)	0 / 25 (0.00%)	0 / 9 (0.00%)	0 / 45 (0.00%)	1 / 16 (6.25%)	0 / 5 (0.00%)	0 / 16 (0.00%)	0 / 34 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	1 / 39 (2.56%)	2 / 31 (6.45%)	0 / 25 (0.00%)	0 / 9 (0.00%)	1 / 45 (2.22%)	1 / 36 (2.78%)	0 / 5 (0.00%)	0 / 16 (0.00%)	2 / 34 (5.88%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	3	0	0	1	1	0	0	2	0	0	0
Oropharyngeal pain
subjects affected / exposed	2 / 39 (5.13%)	0 / 31 (0.00%)	1 / 25 (4.00%)	0 / 9 (0.00%)	5 / 45 (11.11%)	0 / 36 (0.00%)	0 / 5 (0.00%)	0 / 16 (0.00%)	1 / 34 (2.94%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	2	0	1	0	5	0	0	0	1	0	0	0
Rhinorrhoea
subjects affected / exposed	0 / 39 (0.00%)	0 / 31 (0.00%)	0 / 25 (0.00%)	0 / 9 (0.00%)	0 / 45 (0.00%)	2 / 36 (5.56%)	0 / 5 (0.00%)	0 / 16 (0.00%)	0 / 34 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0	0	0	0
Nasal congestion
subjects affected / exposed	0 / 39 (0.00%)	1 / 31 (3.23%)	0 / 25 (0.00%)	0 / 9 (0.00%)	0 / 45 (0.00%)	1 / 36 (2.78%)	0 / 5 (0.00%)	1 / 16 (6.25%)	0 / 34 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	1	0	1	0	0	0	0
Skin and subcutaneous tissue disorders
Acne
subjects affected / exposed	1 / 39 (2.56%)	2 / 31 (6.45%)	1 / 25 (4.00%)	0 / 9 (0.00%)	0 / 45 (0.00%)	0 / 36 (0.00%)	0 / 5 (0.00%)	0 / 16 (0.00%)	0 / 34 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	3	1	0	0	0	0	0	0	0	0	0
Rash
subjects affected / exposed	0 / 39 (0.00%)	0 / 31 (0.00%)	0 / 25 (0.00%)	0 / 9 (0.00%)	1 / 45 (2.22%)	0 / 36 (0.00%)	0 / 5 (0.00%)	1 / 16 (6.25%)	0 / 34 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	0	1	0	0	0	0
Renal and urinary disorders
Leukocyturia
subjects affected / exposed	3 / 39 (7.69%)	1 / 31 (3.23%)	3 / 25 (12.00%)	2 / 9 (22.22%)	1 / 45 (2.22%)	3 / 36 (8.33%)	1 / 5 (20.00%)	0 / 16 (0.00%)	0 / 34 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	3	2	4	2	1	4	1	0	0	1	0	0
Haematuria
subjects affected / exposed	1 / 39 (2.56%)	1 / 31 (3.23%)	1 / 25 (4.00%)	1 / 9 (11.11%)	1 / 45 (2.22%)	0 / 36 (0.00%)	0 / 5 (0.00%)	0 / 16 (0.00%)	1 / 34 (2.94%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	1	1	1	1	0	0	0	1	0	0	0
Hydronephrosis
subjects affected / exposed	0 / 39 (0.00%)	2 / 31 (6.45%)	0 / 25 (0.00%)	0 / 9 (0.00%)	1 / 45 (2.22%)	0 / 36 (0.00%)	0 / 5 (0.00%)	0 / 16 (0.00%)	2 / 34 (5.88%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	2	0	0	1	0	0	0	2	0	0	0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	2 / 39 (5.13%)	1 / 31 (3.23%)	0 / 25 (0.00%)	0 / 9 (0.00%)	0 / 45 (0.00%)	0 / 36 (0.00%)	0 / 5 (0.00%)	0 / 16 (0.00%)	1 / 34 (2.94%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	2	1	0	0	0	0	0	0	1	0	0	0
Neck pain
subjects affected / exposed	1 / 39 (2.56%)	0 / 31 (0.00%)	0 / 25 (0.00%)	1 / 9 (11.11%)	0 / 45 (0.00%)	0 / 36 (0.00%)	0 / 5 (0.00%)	0 / 16 (0.00%)	0 / 34 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	1	0	0	0	0	0	0	0	0
Infections and infestations
Urinary tract infection
subjects affected / exposed	13 / 39 (33.33%)	9 / 31 (29.03%)	5 / 25 (20.00%)	1 / 9 (11.11%)	22 / 45 (48.89%)	6 / 36 (16.67%)	0 / 5 (0.00%)	4 / 16 (25.00%)	6 / 34 (17.65%)	1 / 3 (33.33%)	1 / 4 (25.00%)	0 / 4 (0.00%)
occurrences all number	22	12	7	1	33	8	0	6	7	1	1	0
Bacteriuria
subjects affected / exposed	7 / 39 (17.95%)	5 / 31 (16.13%)	5 / 25 (20.00%)	1 / 9 (11.11%)	9 / 45 (20.00%)	2 / 36 (5.56%)	0 / 5 (0.00%)	3 / 16 (18.75%)	4 / 34 (11.76%)	2 / 3 (66.67%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	12	10	10	1	15	3	0	3	8	2	0	0
Pharyngitis
subjects affected / exposed	4 / 39 (10.26%)	3 / 31 (9.68%)	0 / 25 (0.00%)	0 / 9 (0.00%)	3 / 45 (6.67%)	2 / 36 (5.56%)	0 / 5 (0.00%)	1 / 16 (6.25%)	0 / 34 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)
occurrences all number	4	3	0	0	3	2	0	1	0	0	0	1
Nasopharyngitis
subjects affected / exposed	1 / 39 (2.56%)	0 / 31 (0.00%)	4 / 25 (16.00%)	0 / 9 (0.00%)	2 / 45 (4.44%)	3 / 36 (8.33%)	0 / 5 (0.00%)	0 / 16 (0.00%)	1 / 34 (2.94%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)
occurrences all number	1	0	4	0	2	3	0	0	1	0	0	1
Gastroenteritis
subjects affected / exposed	3 / 39 (7.69%)	1 / 31 (3.23%)	0 / 25 (0.00%)	2 / 9 (22.22%)	2 / 45 (4.44%)	0 / 36 (0.00%)	0 / 5 (0.00%)	1 / 16 (6.25%)	1 / 34 (2.94%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	3	2	0	3	2	0	0	1	1	0	0	0
Bronchitis
subjects affected / exposed	3 / 39 (7.69%)	0 / 31 (0.00%)	1 / 25 (4.00%)	1 / 9 (11.11%)	1 / 45 (2.22%)	0 / 36 (0.00%)	0 / 5 (0.00%)	0 / 16 (0.00%)	0 / 34 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	3	0	1	1	1	0	0	0	0	0	0	0
Cystitis
subjects affected / exposed	0 / 39 (0.00%)	0 / 31 (0.00%)	0 / 25 (0.00%)	1 / 9 (11.11%)	1 / 45 (2.22%)	0 / 36 (0.00%)	0 / 5 (0.00%)	1 / 16 (6.25%)	0 / 34 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	1	0	0	1	0	0	0	0
Gastroenteritis viral
subjects affected / exposed	0 / 39 (0.00%)	0 / 31 (0.00%)	1 / 25 (4.00%)	1 / 9 (11.11%)	1 / 45 (2.22%)	0 / 36 (0.00%)	0 / 5 (0.00%)	0 / 16 (0.00%)	0 / 34 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	1	1	0	0	0	0	0	0	0
Viral infection
subjects affected / exposed	1 / 39 (2.56%)	1 / 31 (3.23%)	0 / 25 (0.00%)	0 / 9 (0.00%)	0 / 45 (0.00%)	2 / 36 (5.56%)	0 / 5 (0.00%)	0 / 16 (0.00%)	0 / 34 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	1	0	0	0	2	0	0	0	0	0	0
Tinea capitis
subjects affected / exposed	0 / 39 (0.00%)	0 / 31 (0.00%)	0 / 25 (0.00%)	1 / 9 (11.11%)	0 / 45 (0.00%)	0 / 36 (0.00%)	0 / 5 (0.00%)	0 / 16 (0.00%)	0 / 34 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0
Sinusitis
subjects affected / exposed	0 / 39 (0.00%)	2 / 31 (6.45%)	1 / 25 (4.00%)	0 / 9 (0.00%)	2 / 45 (4.44%)	0 / 36 (0.00%)	0 / 5 (0.00%)	0 / 16 (0.00%)	0 / 34 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	2	1	0	4	0	0	0	0	0	0	0
Asymptomatic bacteriuria
subjects affected / exposed	2 / 39 (5.13%)	1 / 31 (3.23%)	0 / 25 (0.00%)	1 / 9 (11.11%)	1 / 45 (2.22%)	0 / 36 (0.00%)	0 / 5 (0.00%)	0 / 16 (0.00%)	0 / 34 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	2	1	0	1	1	0	0	0	0	0	0	0
Influenza
subjects affected / exposed	2 / 39 (5.13%)	0 / 31 (0.00%)	1 / 25 (4.00%)	0 / 9 (0.00%)	4 / 45 (8.89%)	1 / 36 (2.78%)	0 / 5 (0.00%)	0 / 16 (0.00%)	1 / 34 (2.94%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)
occurrences all number	2	0	1	0	4	1	0	0	1	0	0	1
Upper respiratory tract infection
subjects affected / exposed	2 / 39 (5.13%)	0 / 31 (0.00%)	1 / 25 (4.00%)	0 / 9 (0.00%)	2 / 45 (4.44%)	2 / 36 (5.56%)	0 / 5 (0.00%)	0 / 16 (0.00%)	0 / 34 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	3	0	1	0	4	3	0	0	0	0	0	0

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Number of subjects exposed in the OnabotulinumtoxinA 200 U (Treatment Cycle 2) arm group is based on the female population.

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Were there any global substantial amendments to the protocol? Yes

04 Oct 2013

Amendment 1 - The following changes were implemented with Amendment 1: Provided clarifications and guidance to investigators regarding entry criteria, study procedures, and prohibited medications/treatments. In addition, the following procedures were added to the protocol: • Addition of renal function assessment [estimated glomerular filtration rate (eGFR)] • Added form for collecting ‘Reason for Requesting Retreatment’ at week 12 and later.

05 May 2016

Amendment 2 - The following changes were implemented with Amendment 1: Modified the inclusion criteria to change the minimum age to 5 years old from 8 years old and to include dosing information for a younger patient population. In addition, an update was made to the criteria which the investigator should consider when determining if a patient had a urinary track infection (UTI). According to the protocol, an adverse event of UTI was defined as ‘a symptomatic UTI that required treatment in the opinion of the investigator’. The protocol also indicated that if urinalysis/culture results were reported which, in the opinion of the investigator, were considered clinically significant but did not fulfill the definition of UTI, the findings were to be recorded as adverse events (e.g., bacteriuria, leukocyturia). In addition, the investigator was required to describe the criteria used for qualifying ‘leukocyturia’ as an adverse event.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: Long-term Extension Study of BOTOX® in the Treatment of Urinary Incontinence Due to Neurogenic Detrusor Overactivity in Patients 5 to 17 Years of Age

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change From Study Baseline in the Daily Normalized Daytime Average Number of Urinary Incontinence Episodes in Treatment Cycle 1

Primary: Change From Study Baseline in the Daily Normalized Daytime Average Number of Urinary Incontinence Episodes in Treatment Cycle 1

Primary: Change From Study Baseline in the Daily Normalized Daytime Average Number of Urinary Incontinence Episodes in Treatment Cycle 2

Primary: Change From Study Baseline in the Daily Normalized Daytime Average Number of Urinary Incontinence Episodes in Treatment Cycle 2

Primary: Change From Study Baseline in the Daily Normalized Daytime Average Number of Urinary Incontinence Episodes in Treatment Cycle 3

Primary: Change From Study Baseline in the Daily Normalized Daytime Average Number of Urinary Incontinence Episodes in Treatment Cycle 3

Secondary: Number of Participants with Treatment Emergent Adverse Events (TEAEs) and Serious Treatment Emergent Adverse Events (STEAEs)

Secondary: Number of Participants with Treatment Emergent Adverse Events (TEAEs) and Serious Treatment Emergent Adverse Events (STEAEs)

Secondary: Percentage of Participants with ≥ 50%, ≥ 75%, ≥ 90%, and ≥ 100% Reduction from Baseline in the Number of Normalized Daytime Urinary Incontinence Episodes in Treatment Cycle 1

Secondary: Percentage of Participants with ≥ 50%, ≥ 75%, ≥ 90%, and ≥ 100% Reduction from Baseline in the Number of Normalized Daytime Urinary Incontinence Episodes in Treatment Cycle 1

Secondary: Percentage of Participants with ≥ 50%, ≥ 75%, ≥ 90%, and ≥ 100% Reduction from Baseline in the Number of Normalized Daytime Urinary Incontinence Episodes in Treatment Cycle 2

Secondary: Percentage of Participants with ≥ 50%, ≥ 75%, ≥ 90%, and ≥ 100% Reduction from Baseline in the Number of Normalized Daytime Urinary Incontinence Episodes in Treatment Cycle 2

Secondary: Percentage of Participants with ≥ 50%, ≥ 75%, ≥ 90%, and ≥ 100% Reduction from Baseline in the Number of Normalized Daytime Urinary Incontinence Episodes in Treatment Cycle 3

Secondary: Percentage of Participants with ≥ 50%, ≥ 75%, ≥ 90%, and ≥ 100% Reduction from Baseline in the Number of Normalized Daytime Urinary Incontinence Episodes in Treatment Cycle 3

Secondary: Change from Baseline in Average Urine Volume at First Morning Catheterization in Treatment Cycle 1

Secondary: Change from Baseline in Average Urine Volume at First Morning Catheterization in Treatment Cycle 1

Secondary: Change from Baseline in Average Urine Volume at First Morning Catheterization in Treatment Cycle 2

Secondary: Change from Baseline in Average Urine Volume at First Morning Catheterization in Treatment Cycle 2

Secondary: Change from Baseline in Average Urine Volume at First Morning Catheterization in Treatment Cycle 3

Secondary: Change from Baseline in Average Urine Volume at First Morning Catheterization in Treatment Cycle 3

Secondary: Percentage of Participants with Night Time Urinary Incontinence in Treatment Cycle 1

Secondary: Percentage of Participants with Night Time Urinary Incontinence in Treatment Cycle 1

Secondary: Percentage of Participants with Night Time Urinary Incontinence in Treatment Cycle 2

Secondary: Percentage of Participants with Night Time Urinary Incontinence in Treatment Cycle 2

Secondary: Percentage of Participants with Night Time Urinary Incontinence in Treatment Cycle 3

Secondary: Percentage of Participants with Night Time Urinary Incontinence in Treatment Cycle 3

Secondary: Average Time to Participant's Request for Retreatment

Secondary: Average Time to Participant's Request for Retreatment

Secondary: Average Time to Participant's Qualification for Retreatment

Secondary: Average Time to Participant's Qualification for Retreatment

Secondary: Percentage of Participants with Positive Response on Modified Treatment Benefit Scale (TBS) in Treatment Cycle 1

Secondary: Percentage of Participants with Positive Response on Modified Treatment Benefit Scale (TBS) in Treatment Cycle 1

Secondary: Percentage of Participants with Positive Response on Modified Treatment Benefit Scale (TBS) in Treatment Cycle 2

Secondary: Percentage of Participants with Positive Response on Modified Treatment Benefit Scale (TBS) in Treatment Cycle 2

Secondary: Percentage of Participants with Positive Response on Modified Treatment Benefit Scale (TBS) in Treatment Cycle 3

Secondary: Percentage of Participants with Positive Response on Modified Treatment Benefit Scale (TBS) in Treatment Cycle 3

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
Long-term Extension Study of BOTOX® in the Treatment of Urinary Incontinence Due to Neurogenic Detrusor Overactivity in Patients 5 to 17 Years of Age